Biomedical subjects

R G Azizkhan

Publications and source records attributed to R G Azizkhan.

At least 37 records · Page 2Linked to original sources

PubMed1996

Fetal surgical interventions and the development of the heart in congenital diaphragmatic hernia.

Selective left ventricular hypoplasia is a recognized feature of congenital diaphragmatic hernia (CDH). It is speculated that the herniated viscera act as a space occupying lesion that inhibit normal cardiac development. The purpose of this study was to determine the effect of two separate fetal surgical interventions on subsequent cardiac development in CDH. CDH lambs were created at 80 days gestation and underwent either tracheal ligation (CDH + TL) or diaphragmatic repair (CDH + repair) at 110 days gestation. At term (141 days gestation) the hearts were harvested and fixed in 4% paraformaldehyde solution. Anatomic dissections were performed and component heart weights determined. Fresh specimens were analyzed for DNA and protein content. All weights are expressed in grams/kilogram body weight and all data as mean +/- SEM. All measurements are compared to control and CDH tissues. There were seven CDH lambs, five control lambs, five CDH + TL lambs, and five CDH + repair lambs. There were no differences in body weight (kg) between CDH, CDH + TL, CDH + repair, and control littermates. CDH lambs have significantly decreased total heart (4.88 +/- .25* vs 6.75 +/- .49, P < 0.05), left ventricular (1.65 +/- .11* vs 2.15 +/- .19, P < 0.05), septal (1.29 +/- .11* vs 1.99 +/- .21, P < 0.05), and combined atrial (0.68 +/- .06* vs 1.14 +/- .15, P < 0.05) weights (g/kg lamb) without differences in RV weights (1.26 +/- .07 vs 1.57 +/- .17, P = NS) when compared to littermate controls. No differences were found in total heart (4.82 +/- 0.38 vs 4.88 +/- 0.25), left ventricular (1.48 +/- 0.13 vs 1.65 +/- 0.11), septal (1.26 +/- 0.17 vs 1.29 +/- 0.11), combined atrial weights (0.56 +/- 0.07 vs 0.68 +/- 0.06), and right ventricular (1.52 +/- 0.12 vs 1.26 +/- 0.07) between CDH + TL and CDH lambs. There were no differences in total heart (6.60 +/- 0.29 vs 6.75 +/- 0.49), left ventricular (2.10 +/- 0.15 vs 2.15 +/- 0.19), septal (1.97 +/- 0.18 vs 1.99 +/- 0.21), combined atrial (1.10 +/- 0.10 vs 1.14 +/- 0.15), or right ventricular (1.52 +/- 0.12 vs 1.57 +/- 0.17) weights between CDH + repair and control lambs. LV and RV wall thicknesses (cm), as well as total protein and DNA content, and DNA/total protein ratios were identical in all groups. CDH lambs have a significant reduction in total heart weights mainly caused by hypoplasia of the left ventricle (left ventricular "smallness") and the interventricular septum. Removal of the herniated viscera and repair of the diaphragmatic defect correct this abnormality, but tracheal ligation does not. We speculate that although tracheal ligation reverses pulmonary hypoplasia, the enlarging lungs act as space occupying lesions that adversely affect cardiac development. Further investigations are necessary to determine the functional significance of these findings.

Animals↗

PubMed1996

Chest wall constriction after too extensive and too early operations for pectus excavatum.

BACKGROUND AND METHODS: Since 1990 we have evaluated 12 children and teenagers in whom severe cardiorespiratory symptoms have developed due to failure of chest wall growth after very extensive pectus excavatum operations (removal of five or more ribs) at very early ages (< 4 years). RESULTS: Apparently these extensive procedures have removed or prevented growth center activity, which resulted in restriction of chest wall growth with marked limitation of ventilatory function. The forced vital capacity ranged from 30% to 50% of predicted and the forced expiratory volume in 1 second from 30% to 60%. All patients are symptomatic with mild exercise and cannot compete in running games. Our protocol for critical evaluation includes exercise pulmonary function studies and axial computed tomographic reconstruction. CONCLUSIONS: This report is an alert to recognize such patients and also to recommend delay in operative repair in small children until at least 6 to 8 years of age. The younger the patient the more limited the chest wall resection for pectus excavatum should be. Five of these patients have had a chest cavity expansion operation with encouraging early results.

Adolescent↗

PubMed1996

Decreased pulmonary nitric oxide synthase activity in the rat model of congenital diaphragmatic hernia.

Because nitric oxide (NO) dilates vascular smooth muscle cells, a deficiency of endogenous pulmonary nitric oxide production by nitric oxide synthase (NOS) has been suggested to be involved in the pathophysiology of pulmonary hypertension in congenital diaphragmatic hernia (CDH). Our aim was to determine whether experimentally induced CDH in rats results in a decrease in the synthesis of NO in the lungs. Adult Sprague-Dawley rats were fed 300 mg/kg of nitrofen at 10.5 days' gestation. CDH, control, and sham (dosed with nitrofen, but without CDH) lungs were homogenized at full term (22 days' gestation) for measurement of NOS activity using the 14C-L-arginine to 14C-L-citrulline conversion assay. Western blot analysis with anti-endothelial cell NOS (EC-NOS) monoclonal antibody (mAb) was performed, and NOS expression was measured by densitometry. NOS activity was highest in the pulmonary parenchyma of control rat lungs (0.420 +/- 0.20 fmol/min/mg lung; n = 11), intermediate in sham lungs (0.370 +/- 0.010 fmol/min/mg lung; n = 14), and lowest in CDH lungs (0.300 +/- 0.04 fmol/min/mg lung; n = 12). NOS activity in the CDH and sham lungs was significantly lower than that of control lungs (P < .05). There was no difference in pulmonary NOS activity between sham and CDH lungs. NOS protein expression by Western blot analysis paralleled the observation for NOS activity in all groups, with the highest concentrations in controls, intermediate expression in sham lungs, and lowest expression in CDH lungs. Both NOS expression and NOS activity are significantly decreased in CDH rat lungs. Pulmonary hypertension in this model may be attributable to a deficiency of endogenous NO. This is the first reported study to suggest that decreased NOS activity may result in pulmonary hypertension in CDH.

Animals↗

PubMed1996

Insurance-related differences in the presentation of pediatric appendicitis.

In the pediatric population, there is strong evidence to suggest that a delay in treatment results in an increased risk of appendiceal perforation. However, it is not clear whether this delay arises from the parent seeking medical advice, the referring physician seeking surgical consultation, or the surgeon deciding to operate. To resolve this issue, the authors performed a retrospective chart review of all cases of confirmed acute appendicitis that presented to the pediatric surgical service of the Children's Hospital of Buffalo during a 4-year period (January 1990 through December 1993). All children (< or = 16 years of age) were categorized with respect to type of insurance coverage:Medicaid (or uninsured), health maintenance organization (HMO), or private fee-for-service. Their time until emergency room (ER) presentation, operating room (OR) presentation, and hospital discharge were recorded and compared. Their complications and perforation rates also were noted. Two hundred eighty-eight cases were reviewed. The rate of appendiceal perforation was significantly higher among the Medicaid patients (Medicaid, 44%; HMO, 27%; private, 23%; P < .05); their duration of symptoms before presentation was significantly longer (Medicaid, 47.3 +/- 4.1 hours; HMO, 29.3 +/- 1.9 hours; private, 23.1 +/- 2.5 hours; P < .01), and their hospital stay was longer (Medicaid, 7.9 +/- 0.9 days; HMO, 4.8 +/- 0.27 days; private, 4.6 +/- 0.44 days; P < .01). However, there were no significant differences in the time from presentation to the ER until definitive surgery in the OR. Children covered by Medicaid (or uninsured) presented later, had a higher risk of appendiceal perforation, and required a longer hospital stay. The parents of these children either failed to recognize the significance of their children's symptoms, or delayed seeking medical advice because of financial or logistical reasons. The gatekeeper consultation, required by the health maintenance organizations (HMO) did not result in a delay in presentation or have a negative impact on morbidity. Providing easier access to a primary care physician and improving parental health education/awareness may shorten the time until presentation for the uninsured/Medicaid patient.

Acute Disease↗

PubMed1996

Surfactant rescue in the fetal lamb model of congenital diaphragmatic hernia.

Surfactant therapy given before the onset of ventilation (surfactant prophylaxis) has been shown to improve oxygenation, ventilation, and pulmonary hemodynamics in the lamb model of congenital diaphragmatic hernia (CDH). The aim of this study was to assess the efficacy of surfactant administered after the onset of ventilation ("surfactant rescue"). Ten lambs with surgically created CDH were instrumented, at full term, to measure pulmonary blood flow and pulmonary vascular resistance (PVR). Catheters also were positioned for monitoring of systemic blood pressure and arterial blood gases. The animals were delivered and pressure-ventilated according to a standard protocol (PIP, 30 cm; PEEP, 4 cm; respiratory rate, 60 breaths per minute). After 30 minutes of ventilation, five animals received an intratracheal dose of calf lung surfactant extract (50 mg/kg). The animals were studied for 4 hours. Surfactant rescue had no discernible effect on Pco2, Pco2, or pH. There was an increase in pulmonary blood flow, but it was not significant. The dramatic improvement in oxygenation, ventilation, and pulmonary blood flow found with prophylactic surfactant cannot be reproduced when surfactant is administered as rescue therapy. This indicates that the surfactant is not being delivered adequately, the lungs have already incurred significant barotrauma, and/or the surfactant is being inactivated by alveolar protein. Therefore, the authors suggest that when exogenous surfactant therapy is being considered for the fetus or newborn with CDH, it should be administered as early as possible, preferably before the infant's first breath. Prenatal diagnosis and delivery in a tertiary care center would facilitate this optimum management.

Animals↗

PubMed1996

Neutrophil activation and chemotaxis after in vitro treatment with perfluorocarbon.

The in vitro effects of perfluorocarbon (PFC) on human neutrophil activation and chemotaxis were examined. Neutrophils were incubated, with and without PFC, and were analyzed for chemotaxis through 5-microns and 8-microns pore filters. Neutrophil activation was quantitated by flow cytometry. Activation studies showed that PFC-treated neutrophil samples (n = 6) produced only 39.83% +/- 25.9% (mean +/- SD) of matched control (n = 6) fluorescence. Chemotaxis studies showed that PFC-treated neutrophil samples (n = 8) had migration of only 18.63% +/- 6.5% (of control values) of neutrophils to the outer boundary of the 5-microns filters (n = 8 controls). The 8-microns pore filter migration (n = 8) was similarly low, with a mean outer boundary migration count of only 26% +/- 19.8% of the control (n = 8) value. Thus, neutrophils exposed to perfluorocarbon produce significantly less detectable H2O2 (P < .001) and have a significantly lower chemotactic response (P < .001).

Chemotaxis, Leukocyte↗

PubMed1996

Can cardiac weight predict lung weight in patients with congenital diaphragmatic hernia?

Left ventricular disproportion (decreased left-to-right ventricular internal diameter ratio) has been correlated with fetal or neonatal survival in cases of congenital diaphragmatic hernia (CDH). Because cardiac development is intimately related to lung development in the normally developing fetus, the authors sought to determine whether cardiac weight correlates with lung weight in control and CDH lambs at term. Twenty lambs had CDH created surgically at 80 days' gestation and were sacrificed at term for measurement of lung and heart weight. Nine unoperated lambs served as controls. Analysis of the relationship between heart weight and lung weight was performed for both groups, and regression curves were generated as mean +/- 2 standard deviations (SD) for each group of lambs. All data are expressed in grams. For CDH lambs, the relationship between heart and lung weight is as follows: lung weight = 0.69 x heart weight + 37 g. For control lambs, the equation is: lung weight = -0.004 x heart weight + 135 g. There is no overlap of these regression curves at 2 SD of the mean. The curves differ significantly, and the P value exceeds .05. The results suggest that cardiac weight can be used to predict lung weight in CDH and control lambs at term. The authors speculate that this difference in weight is attributable to underdevelopment of the left ventricle in CDH. Given that left ventricular disproportion has been described as early as the pseudoglandular stage of lung development in human fetuses with CDH, it is hoped that echocardiographic parameters can be used to differentiate the fetuses with adequate lung volume from those whose lung volume is incompatible with extrauterine life. Patients in the latter group may benefit from surgical correction of the diaphragmatic defect in utero.

Analysis of Variance↗

PubMed1996

Surfactant decreases pulmonary vascular resistance and increases pulmonary blood flow in the fetal lamb model of congenital diaphragmatic hernia.

INTRODUCTION: Experiments using animal models of neonatal respiratory distress syndrome have shown a decrease in pulmonary vascular resistance (PVR) with surfactant replacement, whereas studies with the lamb model of congenital diaphragmatic hernia (CDH) have demonstrated improvement in oxygenation and lung mechanics with this therapy. The aim of the present study was to measure the effects of surfactant replacement therapy on the pulmonary hemodynamics of the lamb model of CDH. METHODS: Ten lambs with surgically created CDH and five control lambs were instrumented at term, with the placental circulation intact. Ultrasonic flow probes were positioned around the main pulmonary artery and the common origin of the left and right pulmonary arteries to record total lung and main pulmonary artery blood flow. Catheters were inserted to record systemic, pulmonary, and left atrial pressure. Five CDH animals received 50 mg/kg of surfactant by tracheal instillation just before delivery. All 15 animals were then ventilated for 4 hours. RESULTS: Correcting the surfactant deficiency in the CDH lamb resulted in a significant increase in pulmonary blood flow, a decrease in PVR, and a reduction in right-to-left shunting. These improvements in hemodynamics were associated with a significant improvement in gas exchange over 4 hours. CONCLUSION: The fetal lamb model of CDH has elevated PVR in comparison to controls. Prophylactic surfactant therapy reduces this resistance and dramatically increases pulmonary blood flow while reducing extrapulmonary shunt. A surfactant deficiency may be partially responsible for the persistent pulmonary hypertension in neonates with CDH.

Animals↗

PubMed1996

Tracheal ligation does not correct the surfactant deficiency associated with congenital diaphragmatic hernia.

INTRODUCTION: Experimental tracheal ligation (CDH + TL) has been shown to reverse the profound lung hypoplasia associated with congenital diaphragmatic hernia (CDH) and to normalize gas exchange. The aim of this study was to determine whether this experimental therapy would correct the surfactant deficiency present in the fetal lamb model of CDH. METHODS: The CDH lamb model was created at 80 days' gestation, and tracheal ligation was performed at 110 days. At term, the lambs were delivered and were ventilated for 30 minutes. The lambs were killed, a pressure-volume curve performed, and the lungs lavaged to measure total phospholipid content. Finally, type II pneumocytes were isolated, and surfactant synthesis was assessed by the incorporation of tritiated choline into phosphatidylcholine. RESULTS: CDH + TL resulted in a lung significantly larger than that of CDH alone. The lungs of the former also had better oxygenation and ventilation. However, lung compliance was reduced compared with controls. Total alveolar phospholipid was dramatically lower, with a decrease in the proportion of phosphatidylcholine present. Surfactant synthesis by the isolated type II pneumocyte was significantly impaired. CONCLUSION: Occlusion of the fetal trachea produces a lung comparable in size to a normal control lung. However, broncheoalveolar lavage analysis shows a marked reduction in total phospholipid, with a decrease in surfactant synthesis by the type II pneumocyte. The normalization of gas exchange reported for this animal model may be only a transient phenomenon. Further studies are required to assess the impact of this surfactant deficiency on long-term lung function.

Animals↗

PubMed1996

Teratomas in childhood.

Teratomas are embryonal neoplasms consisting of tissues from at least two of the three germ layers. Teratomas can occur in almost any region of the body and in any organ, but they are most commonly observed in the paraxial and midline locations. Excluding teratomas of the testes, 75% to 80% of teratomas occur in females. Approximately 80% are benign and 20% are malignant. The presenting location of teratomas correlates with patient age. Teratomas occurring in infancy and early childhood are usually extragonadal, whereas older children predominantly present with gonadal teratomas. The most common site of occurrence in neonates is in the sacrococcygeal and presacral region. Prognosis depends on patient's age, the resectability of the tumor, and the presence of metastases or metastatic potential.

Adolescent↗

PubMed1995

Pathophysiology of congenital diaphragmatic hernia. XVI: Elevated pulmonary collagen in the lamb model of congenital diaphragmatic hernia.

The pathophysiologic features of congenital diaphragmatic hernia (CDH) include pulmonary hypoplasia, pulmonary hypertension, surfactant deficiency, and decreased pulmonary compliance. When the surfactant deficiency is corrected using exogenous surfactant therapy, the pulmonary compliance improves, but does not reach normal values. Quasistatic saline pressure-volume measurements, which eliminate the air-liquid interface, confirm that CDH lungs are intrinsically less compliant than control lungs. The authors hypothesized that this abnormal lung compliance results from elevated concentrations of collagen and/or elastin in the lung. Therefore, they measured the collagen and elastin concentrations in CDH and control lung tissue. Also measured was the collagen concentration in the kidney, intestine, and dissected third-generation arterioles, venules, and bronchioles, to characterize further the pathology of CDH. The CDH model was created on the left side of fetuses in pregnant ewes at 80 days' gestation. The fetuses were delivered and killed at 140 days (full term, 145). The concentrations of collagen (as hydroxyproline), elastin, DNA, and total protein were measured using standard techniques. Although there was significantly more collagen per gram of lung tissue in the CDH lungs (1.334 mg/g v 0.885 mg/g in the controls) the elastin concentrations were not different. The elevated collagen concentration was not associated specifically with the conducting airways or vasculature. The collagen concentrations in CDH kidneys and intestines were the same as those of controls. The DNA/total protein ratios in the CDH and control lungs were identical. The results suggest that the elevated collagen concentration was present only in the lungs of CDH lambs, and that it was not attributable to atrophy or hypertrophy of the lungs. Thus, increased collagen in the lung parenchyma may be responsible for the intrinsic stiffness and decreased compliance of the CDH lungs.

Animals↗

PubMed1995

Pathophysiology of congenital diaphragmatic hernia. XII: Amniotic fluid lecithin/sphingomyelin ratio and phosphatidylglycerol concentrations do not predict surfactant status in congenital diaphragmatic hernia.

Abnormal development of the lung in congenital diaphragmatic hernia (CDH) results in a dysfunctional surfactant system. In premature newborns at risk for respiratory distress syndrome, amniotic fluid lecithin/sphingomyelin (L/S) ratios and phosphatidylglycerol (PG) status have been successfully used to predict the surfactant status in the fetus. The objective of this study was to assess the accuracy of L/S ratios and PG in predicting the surfactant status in CDH. The surgically created lamb CDH model was used. Animals were delivered at 140 days' gestation (term 145) and immediately killed. Before delivery amniotic fluid was collected and L/S ratios and PG status were measured. Bronchoalveolar lavage (BAL) was performed and analyzed for total phospholipid and percent phosphatidylcholine (PC). Analysis of the BAL showed that the CDH lungs had both significantly less total phospholipid (CDH 0.10 +/- 0.03 mg/g versus control (CON) 0.76 +/- 0.28 mg/g) and PC (CDH 38 +/- 7.3% versus CON 70 +/- 3.4%) when compared with controls. In contrast the L/S ratios (CDH 2.44 +/- 0.26 versus CON 2.01 +/- 0.32) and PG status (CDH 8.75 +/- 1.01 nmol versus CON 10.2 +/- 0.9) were the same in CDH and control animals. The BAL from the CDH lamb model has a significant surfactant deficiency. Amniotic fluid L/S ratios and PG status were, however, not different between the control and CDH lambs. These results indicate that amniotic fluid L/S ratios and PG do not accurately predict the surfactant status of a fetus with CDH.

Amniotic Fluid↗

PubMed1995

Pathophysiology of congenital diaphragmatic hernia. XI: Anatomic and biochemical characterization of the heart in the fetal lamb CDH model.

AIM: The purpose of this study was to determine whether the presence of bowel in the chest during development in the fetal lamb model of congenital diaphragmatic hernia (CDH) results in structural and/or biochemical hypoplasia of the left venticle. METHODS: The model was created at 80 days' gestation and delivered at term. The hearts were fixed in 4% formaldehyde solution, components weighed, and right ventricular (RV) and left ventricular (LV) wall thicknesses and both aortic (Ao) and pulmonary artery (PA) root diameters were measured. Fresh specimens were analyzed for protein, DNA, hydroxyproline, and elastin content. All CDH measurements are compared with littermate control tissues. RESULTS: There were no differences in body weight (kg) between CDH and control littermates (4.25 +/- 0.26 versus 3.71 +/- 0.24, P = NS). CDH lambs have significantly decreased total heart (4.88 +/- .25 versus 6.75 +/- .49, P < .05), left ventricular (1.65 +/- .11 versus 2.15 +/- .19, P < .05), septal (1.29 +/- .11 versus 1.99 +/- .21, P < .05), and combined atrial (0.68 +/- .06 versus 1.14 +/- .15, P < .05) weights (g/kg lamb) without differences in RV weights (1.26 +/- .07 versus 1.57 +/- .17, P = NS). LV and RV wall thickness, and Ao root diameters (cm) were found to be identical in both CDH and control lambs. However, PA root diameters (0.47 +/- .01 versus 0.38 +/- .01, P < .005) and ductus arteriosus diameters were increased in CDH (0.35 +/- .01 versus 0.22 +/- .02, P < .005). Total protein, DNA collagen, and elastin content and DNA/total protein ratios were identical in RV and LV in both CDH and control lambs. CONCLUSION: Newborn lambs with left-sided CDH have a significantly lower total heart, LV, septal, and atrial weights without differences of RV weight or ventricular wall thicknesses. Given these findings, the unchanged DNA/protein ratio implies that the left ventricle is hypoplastic in CDH. Ao/PA root ratios suggest that LV hypoplasia in utero may result in increased left atrial pressures, decreased right-to-left shunting through the foramen ovale, and increased PA pressures and flow, resulting in increased PA root and ductus arteriosus diameters. This model simulates the clinical data from human fetuses/neonates with CDH. Further investigations are necessary to determine the functional significance of these findings.

Animals↗

PubMed1995

Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children's Cancer Group Surgical Committee.

INTRODUCTION: A multi-institutional study was conducted by the Children's Cancer Group (CCG) to evaluate all soft tissue sarcomas diagnosed within the first month of life. METHODS: A retrospective study by 11 CCG institutions of patient records from 1971 to 1991 were reviewed for demographic data, pathology, therapy, and outcome. RESULTS: 32 neonates with soft tissue sarcomas were identified. There were 21 boys and 11 girls. Pathology was equally divided into three groups: Congenital fibrosarcoma (CFS) (12), rhabdomyosarcoma (RMS) (11), and non-RMS soft tissue sarcomas (NRSTS) (9). Anatomic sites consisted of head/neck (11), extremity (9), trunk (8), pelvis (3), and unknown (2). Overall survival rate was 59% (19/32). CONCLUSION: Soft tissue sarcomas in the neonate comprise three general groups with survival rates dependent on pathology and extent of disease.

Combined Modality Therapy↗

PubMed1995

Spontaneous pneumothorax: a single-institution, 12-year experience in patients under 16 years of age.

OBJECTIVE: To characterize the natural history and outcome of spontaneous pneumothorax in patients under age 16 years. DESIGN: This is a retrospective review in which all patients admitted to the authors' institution (between December 1980 and July 1993) with a diagnosis of spontaneous pneumothorax were included. Information was obtained from the hospital records. SETTING: This study was performed in a university childrens' hospital. PATIENTS: All patients under 16 years with a diagnosis of spontaneous pneumothorax were included. RESULTS: Seventeen patients were admitted and analyzed. Only three admissions were for recurrence. The main symptoms included chest pain (100%), shortness of breath (41%), and cough (6%). Chest tube drainage was successful in 65% of the cases; the median time was 4 days. Two patients had a persistent air leak. An underlying cause was recognized in 42% of cases. Seven operations were necessary, and the mean follow-up periods is 31 months, with no recurrence reported to date. CONCLUSION: Spontaneous pneumothorax occurs in the pediatric population, although it is less common in adults. An underlying pathology is more frequently observed in pediatric patients, but recurrence is less common. Chest tube drainage alone is sufficient treatment for the majority of patients; however, a significant number require some form of surgical intervention.

Adolescent↗

PubMed1995

Diagnosis, management, and outcome of cervicofacial teratomas in neonates: a Childrens Cancer Group study.

The management of cervicofacial teratomas in neonates is often complicated and may result in significant morbidity and death. A Childrens Cancer Group (CCG) retrospective study was conducted to evaluate a multiinstitutional experience with the treatment of these extremely rare neoplasms. Twenty neonates with cervicofacial teratomas, presenting from 1971 to 1994, were identified from nine CCG institutions. Fourteen neonates had cervical teratomas, and six had orofacial teratomas. There were 12 males and eight females. A diagnostic prenatal ultrasound examination was performed in six cases. Life-threatening airway obstruction occurred in seven infants (35%) in the early postnatal period. Two neonates died in the delivery room without ever having their airway secured. Two other infants with a prenatal diagnosis survived only because tracheostomies were performed by pediatric surgeons who were in the delivery room. Three other patients were orally intubated, one after sustaining hypoxic cardiac arrest. Eighteen infants had their primary tumor excised. Three patients required tracheostomy. After resection, two patients had evidence of unilateral recurrent laryngeal nerve injury, and two required prolonged thyroid hormone replacement. Histological examination showed eight mature and seven immature teratomas. Four infants (20%) clearly had malignant lesions. Pulmonary metastases occurred in two patients and contributed to one late death at 6 months of age. The overall survival rate was 85%, and the mean follow-up period was 5 years (range, 2 months to 16 years). Twelve of 17 surviving patients (70%) have had an excellent functional and cosmetic outcome. Four children have varying degrees of developmental delay and mental retardation. Hypoxia at birth was believed to have contributed to these problems in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1995

Pathophysiology of congenital diaphragmatic hernia. X: Localization of nitric oxide synthase in the intima of pulmonary artery trunks of lambs with surgically created congenital diaphragmatic hernia.

The pathophysiology of congenital diaphragmatic hernia (CDH) results from a combination of pulmonary hypoplasia, pulmonary hypertension, and surfactant deficiency. Previously we demonstrated that inhaled nitric oxide (NO), a known vasodilator, only improves oxygenation and decreases pulmonary artery pressures when the lamb model of CDH is pretreated with exogenous surfactant. Nitric oxide synthase (NOS) in endothelial cells is responsible for the production of NO, a mediator of smooth muscle cell relaxation. Pulmonary hypertension in CDH may result from a defect in the endogenous production of NO. Our aim was to determine whether the main pulmonary artery trunks in CDH lambs have NOS immunoreactivity. Cryostat sections of paraformaldehyde-fixed specimens of pulmonary artery and aortic rings from 10 CDH lambs and five control lambs were processed for NADPH-diaphorase activity. Immunolocalization of NOS was studied in paraformaldehyde-fixed sections and compared with serially cut specimens from identical rings that were tested for NADPH-diaphorase activity. Intense NADPH-diaphorase staining was present in the intimal layer (endothelial lining) of the pulmonary artery and aortic rings of both the CDH and control lambs. This activity colocalized with NOS immunoreactivity in all specimens. Both NOS immunoreactivity and NADPH-diaphorase staining were lacking in cartilage, which were used as negative controls. NOS is present in the main pulmonary artery trunks of CDH lambs. To our knowledge, this is the first report of NOS immunoreactivity in CDH. We can only speculate whether this activity is preserved in other areas of the vascular tree in CDH, ie, pulmonary capillaries and veins. Perhaps the pulmonary hypertension in CDH is not caused by an NOS deficiency.

Amino Acid Oxidoreductases↗

PubMed1995

Neonatal Wilms tumor.

Neonatal renal tumors are very rare. We have identified 15 cases of Wilm's tumors diagnosed in the first 30 days of life. The most common presentation was an abdominal mass on routine newborn examination, and three tumors were noted on an antenatal ultrasound. All of the infants underwent primary excision of the tumor. Five infants were not given postoperative chemotherapy after surgical excision. One of these children had a relapse and later died of progressive disease. The remaining children are alive at a median follow-up of 31 months. Eight of the tumors had evidence of nephrogenic rests. More frequent follow-up physical and imaging examinations are indicated in children not given adjuvant chemotherapy or whose tumors show nephrogenic rests.

Combined Modality Therapy↗