Nitrofen induces a redox-dependent apoptosis associated with increased p38 activity in P19 teratocarcinoma cells.

Nitrofen is a diphenyl ether herbicide that produces a spectrum of fetal abnormalities in rodents. To characterize the molecular mechanisms of nitrofen-mediated birth defects at the cellular level, we explored its effects on undifferentiated P19 teratocarcinoma cells. Nitrofen induces a time-dependent cell death of P19 cells that is associated with increases in TUNEL-positivity and caspase-3 cleavage suggesting that nitrofen induces P19 cell apoptosis. In addition, the increase in TUNEL-positive cells was inhibited with zVAD-fmk, suggesting that nitrofen induces a caspase-dependent apoptosis. Nitrofen treatment was associated with increased p38 MAP kinase activity, though pretreatment of cells with multiple p38 inhibitors did not affect nitrofen-mediated caspase-3 cleavage, suggesting caspase-3 cleavage is p38-independent. Nitrofen induced a dose-dependent increase in reactive oxygen species (ROS), which was accompanied by a decrease in the ratio of reduced/oxidized glutathione, indicating that nitrofen alters the cellular redox state of these cells. Furthermore, pretreatment of cells with N-acetyl cysteine gave a dose- and time-dependent reduction of caspase-3 cleavage, supporting the observations that caspase-3 cleavage is cell-redox-dependent. Therefore, nitrofen induces P19 cell apoptosis that is cell-redox-dependent and is associated with increases in p38 activity and ROS and may play a role in nitrofen-mediated birth defects.

Surgical treatment of congenital adrenal hyperplasia.

Unraveling of the genetics of CAH offers the possibility of earlier detection and prenatal treatment or, alternatively, blastocyst embryo selection and eventually in utero gene therapy. Endocrine, surgical, and anesthesia management after birth have improved, leading to a better outcome for these patients. In the authors' experience, early one-stage reconstructive surgery, although demanding, allows one to use all available tissue. Once mastered, the repair is actually technically easier than vaginal pull-through surgery in the adolescent. Patients go through childhood with a body image that is more concordant with normal. Neither the child nor the parents must suffer the anticipation of a major operative intervention at puberty that can cause great emotional stress and that may be more difficult. The authors have encountered situations in late adolescence in which it has been impossible to separate the urogenital sinus from below. Under these circumstances, one can consider a posterior sagittal approach in which the rectum is bivalved to allow one to approach the vagina from below in an attempt to separate it safely from the urethra and to mobilize it to the perineum. It is also feasible to consider fashioning a segment of sigmoid colon as a neovagina, realizing that mucosal drainage needs to be managed daily. The authors have also encountered the rare 46,XX patient raised as a male and committed to the male role. In these cases, the patient can be offered gonadectomy, followed by staged complex hypospadias repair, and surgery to remove Müllerian structures and, if possible, to preserve the vas, followed by prepenile scrotal repair and insertion of testicular prostheses. Children with CAH require a lifetime of care with surgical approaches that are age appropriate. These patients can lead a full and productive life. It is the physician's responsibility to make certain that these children reach their full potential with the least number of interventions, which should be designed and optimized to produce the best possible outcome.

Absolute quantitative autoradiography of low concentrations of [125I]-labeled proteins in arterial tissue.

We developed a method for absolute quantitative autoradiographic measurement of very low concentrations of [125I]-labeled proteins in arterial tissue using Kodak NTB-2 nuclear emulsion. A precise linear relationship between measured silver grain density and isotope concentration was obtained with uniformly labeled standard sources composed of epoxy-embedded gelatin containing glutaraldehyde-fixed [125I]-albumin. For up to 308-day exposures of 1 micron-thick tissue sections, background grain densities ranged from about two to eight grains/1000 micron 2, and the technique was sensitive to as little as about one grain/1000 micron 2 above background, which correspond to a radioactivity concentration of about 2 x 10(4) cpm/ml. A detailed statistical analysis of variability was performed and the sum of all sources of variation quantified. The half distance for spatial resolution was 1.7 micron. Both visual and automated techniques were employed for quantitative grain density analysis. The method was illustrated by measurement of in vivo transmural [125I]-low-density lipoprotein [( 125I]-LDL) concentration profiles in de-endothelialized rabbit thoracic aortic wall.

Current expectations for survival in pediatric burns.

BACKGROUND: Conventional wisdom and published reports suggest that children, particularly those younger than 48 months, have higher mortality rates after burns than young adults. However, coincident with refinements in resuscitation, operative techniques, and critical care, survival rates for children with burns seem to have improved. To document this change and to define current expectations, a review of deaths during two 7-year intervals separated by a decade was done. DESIGN: We examined the clinical course of children who died after admission for care of acute thermal burns during two 7-year intervals: calendar years 1974 to 1980 inclusive (group 1) and 1991 to 1997 inclusive (group 2). Dying children were stratified by total body surface area (TBSA) burned: small (0%-39%), midsize (40%-59%), and large (60%-100%) TBSA burns. Children who arrived with anoxic brain injury or in a moribund state with refractory shock were excluded from analysis (4 children in group 1 and 5 in group 2); 2 of these children in group 2 died and became solid organ donors. SETTING: Regional pediatric burn center. PATIENTS: Six hundred seventy-eight children in group 1 and 1150 children in group 2. MAIN OUTCOME MEASURE: Survival. RESULTS: In children with 0% to 39% TBSA burns, mortality was 0.6% in group 1 and 0% in group 2 (Fisher exact test, P = .04; chi2 test, P = .02). In children with 40% to 59% TBSA burns, mortality was 7.7% in group 1 and 0% in group 2 (Fisher exact test, P = .07; chi2 test, P = .047). In children with 60% to 100% TBSA bums, mortality was 33.3% ingroup 1 and 14.3% in group 2 (Fisher exact test, P = .04; chi2 test, P = .02). Although 59% of the children in group 2 were younger than 48 months, including 55% of those with 40% to 59% TBSA burns and 41% of those with 60% to 100% TBSA burns, there were no deaths in this age group. CONCLUSION: Survival rates after burns have improved significantly for children. At present, most children, even young children and children with large burns, should survive.

Accurate method to study static volume-pressure relationships in small fetal and neonatal animals.

We designed an accurate method to study respiratory static volume-pressure relationships in small fetal and neonatal animals on the basis of Archimedes' principle. Our method eliminates the error caused by the compressibility of air (Boyle's law) and is sensitive to a volume change of as little as 1 microliters. Fetal and neonatal rats during the period of rapid lung development from day 19.5 of gestation (term = day 22) to day 3.5 postnatum were studied. The absolute lung volume at a transrespiratory pressure of 30-40 cmH2O increased 28-fold from 0.036 +/- 0.006 (SE) to 0.994 +/- 0.042 ml, the volume per gram of lung increased 14-fold from 0.39 +/- 0.07 to 5.59 +/- 0.66 ml/g, compliance increased 12-fold from 2.3 +/- 0.4 to 27.3 +/- 2.7 microliters/cmH2O, and specific compliance increased 6-fold from 24.9 +/- 4.5 to 152.3 +/- 22.8 microliters.cmH2O-1.g lung-1. This technique, which allowed us to compare changes during late gestation and the early neonatal period in small rodents, can be used to monitor and evaluate pulmonary functional changes after in utero pharmacological therapies in experimentally induced abnormalities such as pulmonary hypoplasia, surfactant deficiency, and congenital diaphragmatic hernia.

Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure.

HYPOTHESIS: Extracorporeal membrane oxygenation (ECMO) is effective in nonneonatal acute respiratory failure under certain circumstances. DESIGN: Retrospective medical record review. SETTING: The intensive care unit of a tertiary care hospital. PATIENTS: Thirty-four nonneonatal patients (mean age, 22 years; range, 8 days to 56 years), with ratios of the PaO2 to the fraction of inspired oxygen persistently below 70, who were treated with ECMO after maximal ventilator therapy had failed (mean time of ventilator therapy, 6.9 days; range, 1-41 days). The mean ECMO duration was 304 hours (range, 56-934 hours). Patients were grouped into 7 categories based on their diagnosis: sepsis or sepsis syndrome (n = 3), bacterial or fungal pneumonia (n = 10), viral pneumonia (n = 5), trauma or burn (n = 2), inhalation injury without burn (n = 1), immunocompromised state (due to transplantation or chemotherapy) (n = 8), and acute respiratory failure of unknown origin (n = 5). MAIN OUTCOME MEASURE: Survival to hospital discharge following ECMO therapy. RESULTS: Overall survival was 53% (18 patients). All 6 patients (100%) with viral pneumonias or isolated inhalation injuries survived. Of 13 patients with bacterial pneumonia, sepsis, or sepsis syndrome not complicated by multiorgan failure, 10 (77%) survived. In contrast, all but 1 of the immunocompromised patients died. Survival in patients who were intubated for less than 9 days before ECMO was 64%, whereas survival fell precipitously to 22% for patients who experienced mechanical ventilation for 9 or more days before the implementation of ECMO. Finally, the proportion of patients who died while receiving ECMO therapy was greater when the ECMO duration exceeded 300 hours (62% vs. 38%; P<.05). CONCLUSIONS: Nonneonatal survival with ECMO therapy is strongly dependent on the diagnosis. Pre-ECMO intubation for less than 9 days had little effect on survival. Survival rates decreased when the length of time of receiving ECMO exceeded 300 hours.

Evaluation of the infant who has ambiguous genitalia, and principles of operative management.

Infants and children with ambiguous genitalia pose challenging diagnostic and therapeutic issues for the clinician. Success depends on rapid and precise diagnosis, appropriate gender assignment, proper medical therapy, and meticulous surgical technique. A well-trained multispecialty clinical team is essential. The major disease categories include chromosomal abnormalities, excessive androgen syndromes, and deficient androgen syndromes. The specific diseases involved are described in this article, as well as the diagnostic and therapeutic considerations for each.

Toward understanding the developmental anatomy of congenital diaphragmatic hernia.

The pathway of abnormal embryonic development leading to congenital diaphragmatic hernia (CDH) is incompletely understood. Using a nitrofen-induced model of left CDH in rats, sequential stages of development were analyzed by scanning electron microscopy. Abnormal development patterns were observed in the cells comprising the posthepatic mesenchymal plate and the adjacent liver. The septum transversum did not appear to be involved. In this article, the authors theorize that a disturbed "balance of cell growth" is responsible for the creation of the diaphragmatic defect.

Management of the high-risk pediatric burn patient.

BACKGROUND/PURPOSE: Inhalation injury, flame burn exceeding 30%, and age under 48 months all have been cited as independent risk factors for mortality; the combination of all 3 risk factors is unusual. The authors have experienced an overall reduction in mortality rate and chose to examine this high-risk group to define techniques useful in improving outcome in pediatric burns. METHODS: A review was done of children with all 3 risk factors over a recent 9-year interval. All were treated with a system of care emphasizing precise fluid repletion, early wound excision and closure, and avoidance of injurious pulmonary inflating pressures and concentrations of oxygen. Data are expressed as mean +/- SD. RESULTS: There were 26 children admitted with all 3 risk factors. Their average age was 2.1 +/- 1.1 years (range, 5 weeks to 3.7 years), and burn size was 61% +/- 21% (range, 30% to 98%) of the body surface. All required mechanical ventilation for an average of 28 +/- 4.5 days (range, 7 to 74 days). Two children underwent tracheostomy; all others were treated with protracted oral intubation. Inhaled nitric oxide (NO) was used in 3 children, all of whom were considered for extracorporeal membrane oxygenator (ECMO) support, although none went on to ECMO. Only 7 children (27%) never had any bacteremia. Ventilator-related pneumonia occurred in 8 children (31%). Total lengths of stay, including acute and rehabilitation hospitalizations, averaged 105 +/- 10 days (1.87 +/- 0.2; range, 0.66 to 4.8 days per percent burn). After exclusion of 1 child with a 98% third-and fourth-degree burn, pre-hospital cardiac arrest, and anoxic brain injury who had support withdrawn at 6 hours, all children survived to discharge; 23 followed up in our clinic currently are alive and well with no overt residual respiratory insufficiency. CONCLUSION: A high rate of survival can be expected in young children with large burns and inhalation injury.

Combined antenatal thyrotropin-releasing hormone and low-dose glucocorticoid therapy improves the pulmonary biochemical immaturity in congenital diaphragmatic hernia.

The lungs of patients born with severe congenital diaphragmatic hernia (CDH) are biochemically and morphologically immature. Because antenatal glucocorticoid therapy can accelerate pulmonary maturation in premature neonates who have respiratory distress syndrome, we hypothesized that it may correct the pulmonary biochemical and morphological immaturity associated with CDH. We showed in previous experimental studies that antenatal low-dose dexamethasone improved the biochemical and morphological parameters of pulmonary immaturity in rats that had severe CDH. Somatic and pulmonary growth were inhibited with high doses of dexamethasone. In the present study, we examined the effects of antenatal low-dose dexamethasone and thyrotropin-releasing hormone (TRH), alone or in combination, on the pulmonary maturation in CDH. Combined antenatal low-dose dexamethasone and TRH significantly reduced mean lung glycogen concentration (P = .001), and increased mean disaturated phosphatidylcholine content (P < .005) to better than that observed with either therapy alone, without changing mean body or lung weight. Combined TRH and low-dose glucocorticoid as an antenatal therapy may reduce the morbidity and mortality of CDH.

Prenatal hormonal therapy improves pulmonary compliance in the nitrofen-induced CDH rat model.

Neonates with congenital diaphragmatic hernia (CDH) experience a high mortality despite intensive medical and surgical management. The associated pulmonary hypoplasia is accompanied by an underlying biochemical deficiency that bears similarity to respiratory distress syndrome (RDS) in the premature newborn. Using therapies extrapolated from those used to treat RDS, the authors have previously shown correction of the immature pulmonary biochemical indices in the nitrofen rat CDH model. This study investigates the functional and histological outcome of prenatal hormone therapy on CDH rats. Compared with saline-treated CDH controls, dexamethasone-treated CDH animals achieved significant increases in lung distensibility (P = .0006) and functional residual capacity (P = .004); CDH rats treated with combined dexamethasone and thyrotropin-releasing hormone (TRH) showed improved functional residual capacity (P = .043) and alveolar stability (P = .025); CDH animals treated with TRH alone (TRH-CDH) showed no improvement in any parameter tested. Histologically, the lungs from dexamethasone- and dexamethasone-TRH-treated CDH animals showed changes that included narrow septal walls, increased air saccule size, and thinning of the pulmonary interstitium compared with the lungs of saline or TRH-CDH rats, which were developmentally arrested at the canalicular stage. Lung weights and lung weight-body weights ratios were similar in all CDH rats, confirming that treatment did not impair pulmonary growth. These results support the potential clinical use of prenatal pharmacological therapies to treat human fetuses with prenatally diagnosed CDH.

Embryonic cell death patterns associated with nitrofen-induced congenital diaphragmatic hernia.

The offspring of pregnant Sprague-Dawley rats exposed to nitrofen on gestational day 9.5 develop left-sided congenital diaphragmatic hernia (CDH). Twenty-four hours after treatment, on day 10.5, supravital staining with Nile blue sulfate and histological examination showed bilateral excessive cell death in cervical somites 2 through 4. After 48 hours, on day 11.5, cell death was absent in the cervical somites but was apparent in the mesoderm adjacent to the somites in the septum transversum and in the developing sympathetic ganglia adjacent to the dorsal aortae. Cell death was not apparent in the foregut or lung primordia on either day 10.5 or 11.5. The incidence of nitrofen-exposed embryos with such patterns of cell death closely paralleled that of left-sided CDH in similarly treated day 21.5 fetuses. Control animals treated with olive oil had normal programmed cell death patterns in the regions of interest and had no evidence of CDH on day 21.5. It is possible that these patterns of excessive cell death early in gestation may play a role in the genesis of diaphragmatic hernia. Mesoderm derived from cervical somites 3 through 5 contributes to the diaphragmatic anlage and forms the major portion of the muscle of the diaphragm. Because nitrofen damages mesodermal cell populations in cervical somites 2 through 4 and in the mesenchyme adjacent to the septum transversum 24 to 48 hours after administration, the authors propose that damage to these populations may reduce progenitor cells needed to populate the diaphragmatic anlage, thereby hindering pleuro-peritoneal canal closure.(ABSTRACT TRUNCATED AT 250 WORDS)

High-frequency intratracheal pulmonary ventilation: improved gas exchange at lower airway pressures.

PURPOSE: Conventional ventilation in the neonatal intensive care unit causes iatrogenic injury to fragile newborn lungs, especially those with preexisting pathology or prematurity. Intratracheal pulmonary ventilation (ITPV), developed by Dr Theodor Kolobow and associates at the National Institutes of Health (NIH), incorporates a continuous flow of humidified gas through a reverse thrust catheter positioned at the distal end of the endotracheal tube. In animal studies ITPV was shown to facilitate gas exchange at low peak pressures by reducing physiological dead space, facilitating exhalation, and enhancing CO2 elimination. The specific aims of this project were (1) to invent a new ITPV-specific ventilator; (2) to optimize gas exchange in a newborn animal model at low airway pressures using higher frequency ITPV; and (3) to demonstrate efficacy and improved ventilation at lower airway pressures in a prematurity model. METHODS: (1) A new ventilator had to be constructed. The first prototype is microprocessor driven, incorporating controls for flow, pressures, and concentrations of gases. The ventilator has the capability to vary Fio2, respiratory rate (0 to 15 Hz), and inspiratory-expiratory I:E ratio. (2) Prototype testing was performed. Newborn lambs (n = 3, 6 to 7 kg) underwent tracheotomy and placement of arterial and venous lines. Lambs were initially supported on conventional mechanical ventilation (CMV). Animals were allowed to achieve steady state with measurements of baseline vital signs, arterial blood gases, and ventilatory settings. ITPV was instituted at a rate of 100 breaths per minute and flow adjusted to achieve lower peak carinal pressures than obtainable on conventional ventilation. In a stepwise fashion, respiratory rate, I:E ratio, and ITPV flows were varied while initially maintaining Paco2 constant, and then allowing improvement. (3) These experiments were repeated in preterm lambs (n = 6, 1.8 to 3.6 kg). RESULTS: At the time of transition from CMV to ITPV (rate, 100, I:E, 1:3), gas exchange was maintained despite a documented drop in average peak carinal pressure for the newborn lambs from 28.3 cm H2O on CMV to 10.3 cm H2O on ITPV (P = .028). The average peak carinal pressure fell even further at higher ITPV rates with adjustments in I:E ratio. For the premature lambs, peak carinal pressures also fell significantly on ITPV (44 to 32 cm H2O, P = .002) with corresponding significant improvement in ventilation (Paco2 from 52.2 to 31.9 mm Hg, P = .029). CONCLUSIONS: (1) Our new ITPV ventilator operates at rates and I:E ratios previously unobtainable. (2) In newborn and premature lambs ITPV functions most effectively at higher rates with higher gas flow rates and with longer exhalation, providing significantly improved gas exchange at significantly lower peak carinal pressures. (3) ITPV may prove beneficial in achieving gas exchange in newborns while avoiding barotrauma. Based on these data, we have initiated human clinical studies of ITPV in newborns with congenital diaphragmatic hernia or prematurity to improve gas exchange and reduce barotrauma in the neonatal intensive care unit.

Surgical evaluation and management of refractory constipation in older children.

Chronic constipation is a common childhood problem that accounts for 3% to 5% of pediatric visits and 10% to 25% of referrals to pediatric gastroenterologists. The etiology of constipation can be elusive, and extensive investigation often fails to identify a specific cause. The authors conducted a 5-year retrospective review of the patients referred for deep transanal rectal biopsy to determine the usefulness of this procedure in the evaluation and subsequent surgical management of refractory constipation. Specimens obtained by transanal rectal biopsy established a diagnosis for 30 of the 70 patients, and 17 of these 30 had subsequent procedures in the treatment of their constipation. The authors conclude that transanal rectal biopsy identifies a significant number of patients with previously unidentified neuroenteric disorders who may benefit from additional surgery in the treatment of constipation refractory to medical management.

Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia.

BACKGROUND/PURPOSE: Recurrent pulmonary hypertension in the neonatal population is an unusual event with dire consequences. Pulmonary hypertension seen in association with pulmonary hypoplasia may be refractory to conventional medical management. The effect of the calcium channel antagonist diltiazem was studied in five patients with severe pulmonary hypertension. METHODS: A retrospective review of the hospital records was performed to determine the efficacy of diltiazem for refractory pulmonary hypertension. All five patients experienced and did not respond to maximal conventional therapy, which included inhaled nitric oxide, intravenous nitrates, and extracorporeal membrane oxygenation (ECMO). Right ventricular pressures were determined by transthoracic echocardiograms and were used to document improvement in the pressure gradients. Statistical analyses were performed using a paired Student's ttest. A P value of less than .05 was considered significant. RESULTS: Diltiazem significantly reduced the right ventricular systolic pressure (RVSP) from 82 +/- 8.4 mm Hg to 58.4 +/- 7 mm Hg (P = .008). Two patients died; one had a large ventricular septal defect, and the other suffered multisystem organ failure secondary to sepsis. The surviving patients were weaned off diltiazem and did not experience recurrent pulmonary hypertension. CONCLUSIONS: In cases of pulmonary hypoplasia with recurrent pulmonary hypertension, diltiazem may be considered as a therapy. A multicenter prospective trial is advocated.

Prenatal vitamin E treatment improves lung growth in fetal rats with congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia. To discover factors that would accelerate fetal lung growth, the authors developed models of hypoplasia, found that antioxidants improved lung growth in vitro, and then proceeded to in vivo studies. METHODS: Timed-pregnant rats were fed nitrofen (100 mg) on gestational day 9.5 (term, 22), and fetal lungs were harvested at day 13.5 and placed in organ culture in serum-free media with (n = 10) or without (n = 9) additional vitamin E (0.134 IU/mL). Camera lucida tracings were made daily on live, unstained lungs for 4 days, scanned, digitized, and analyzed for multiple growth parameters. Similar nitrofen-exposed rats were fed an optimized total dose of 150 IU vitamin E (n = 19) or olive oil (n = 13) from days 16.5 to 20.5, and fetal lungs were harvested at day 21.5, weighed and fixed for histology, or homogenized and biochemically analyzed. RESULTS: Vitamin E accelerated hypoplastic fetal lung growth in vitro as measured by area, perimeter, lung bud count, perimeter over square root area, and fractal dimension. In vivo vitamin E significantly increased lung weights, total DNA, and protein contents. CONCLUSIONS: Vitamin E accelerates hypoplastic fetal rat lung growth and complexity in vitro, and prenatal vitamin E treatment in vivo improves pulmonary hypoplasia in fetal rats with CDH.

Tracheal resection and reanastomosis in the neonatal period.

BACKGROUND/PURPOSE: Severe congenital tracheal stenosis is rare. Most of these can be managed conservatively before elective repair. Focal tracheal stenosis has been treated with resection of the involved trachea and primary reanastomosis in older infants. The authors found no reports of repair of this lesion in neonates. Two patients are presented with severe respiratory failure on the first day of life that required extracorporeal life support (ECLS) who underwent successful tracheal resection and reanastomosis (TRR) during the first week of life. METHODS: A retrospective review was conducted. RESULTS: Both babies had severe pulmonary hypertension and carbon dioxide retention despite maximal therapy and were placed on ECLS shortly after transfer. One had an isolated stenosis of the upper trachea, and the other had agenesis of the right lung, esophageal atresia with tracheoesophageal fistula, and a tracheal stenosis at the end of a short trachea with a long, narrow left bronchus. Both underwent diagnostic studies and had surgical repair while on ECLS at day 3 and 7 of life without bleeding complications. They were weaned off ECLS 1 and 8 days after surgery. One patient was extubated and did well. The other was extubated transiently, but required a tracheostomy because of left mainstem bronchomalacia. Both are alive and well at 18 and 38 months of age, with no narrowing of the repairs. CONCLUSION: In the setting of severe respiratory failure requiring ECLS support, TRR can be performed safely and successfully in the neonate with focal tracheal stenosis.

Intratracheal pulmonary ventilation and congenital diaphragmatic hernia: a report of two cases.

Previous studies from our institution have shown that neonates with congenital diaphragmatic hernia (CDH), whose best postductal PaO2 (BPDPO2) was less than 100 mm Hg while on maximal conventional mechanical ventilation (CMV), had a mortality exceeding 90%. When combined with extracorporeal membrane oxygenation (ECMO), the mortality rose to 100% in those infants who developed hypercarbia following decannulation. Historically, those patients have required increasing ventilator support, leading to iatrogenic lung damage, and eventual death. Intratracheal pulmonary ventilation (ITPV) using the reverse thrust catheter (RTC) developed by Kolobow incorporates a continuous flow of humidified gas through a reverse Venturi catheter positioned at the distal end of the endotracheal tube. In animal studies, ITPV was shown to result in a reduced physiological dead-space (VD), to facilitate expiration, and to enhance CO2 elimination. In our current study, we have applied ITPV in two neonates with CDH who could not be weaned from ECMO because of uncontrollable hypercapnia, and who met above criteria for 100% mortality. In both cases, ITPV restored normal PaCO2 at low peak inspiratory pressure (PIP) with a substantial decrease in VD. We believe ITPV is suited to ventilating newborns with CDH in whom barotrauma is known to be common. Beyond its present use, ITPV may be useful to ventilate children with other forms of respiratory failure, and should be so considered along with other now available methods of mechanical pulmonary ventilation.

Experience with abdominal wall closure for patients with congenital diaphragmatic hernia repaired on ECMO.

Congenital diaphragmatic hernia (CDH) and its attendant lack of abdominal domain can create major technical challenges with respect to diaphragmatic and abdominal wall reconstruction, especially in seriously ill infants who require extracorporeal membrane oxygenation (ECMO). The authors reviewed the medical records of all infants with CDH repaired on ECMO at their institution (group 1, 15 patients), and compared them with infants having CDH repair before ECMO (group 2, 20 patients) and with those who had CDH repair but did not require ECMO (group 3, 15 patients). Thirty-seven of 50 patients survived (74%): 10 in group 1, 12 in group 2, and all 15 in group 3. There was a statistically significant difference (P < .001) with respect to the requirement of a polytetrafluoroethylene (PTFE) diaphragmatic patch for patients in group 1 versus those in both groups 2 and 3. There was also a significant difference in the number of patients in whom the abdomen could not be closed (P < .001 for group 1 v groups 2 and 3). Infants who require ECMO before CDH repair are more likely to have large diaphragmatic defects that require prosthetic reconstruction, and abdominal wall closure problems resulting from loss of abdominal domain, which further complicate the management of the physiological derangements from pulmonary hypoplasia and persistent pulmonary hypertension.

Posterior mediastinal masses.

Solid mediastinal masses in infancy and childhood occur most frequently in the posterior mediastinum. From 1972 to 1989, 63 patients presented with a posterior mediastinal mass. The median age at diagnosis was 6 years (range, 1 day to 26 years). Thirty patients were female. Forty-five percent of the patients presented with respiratory symptoms or chest pain; 13% had neurologic symptoms, one half of which were related to spinal cord compression; and 5% had a palpable mass. In 32% of patients the mass was an incidental finding. The tumors were of neurogenic origin in 89% of patients, of which neuroblastoma was the most common. Of all patients with posterior mediastinal masses, 60% had malignant tumors. Median follow-up for 62 of 63 evaluable patients was 45 months (range, 1 to 289 months). One patient was lost to follow-up. Of the 62 patients followed, 84% are alive and free of disease. All but 4 of the 32 patients with neuroblastoma are alive and free of disease with a median follow-up of 73 months (range, 7 to 289 months). Patients with neuroblastoma who were diagnosed in the first year of life had a significantly better survival pattern than those presenting after the first year. There were seven deaths in the series: four from neuroblastoma, two from primitive neuroectodermal tumor, and one from malignant schwannoma. Preoperative diagnostic evaluation of a posterior mediastinal mass should include posteroanterior and lateral chest roentgenograms, and either CT or MRI of the chest and abdomen to assess the extent of the mass.(ABSTRACT TRUNCATED AT 250 WORDS)