Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A full-term neonate with a left-sided congenital diaphragmatic hernia (CDH) was ventilated mechanically by high-frequency oscillatory ventilation (HFOV). Despite inhaled nitric oxide (iNO) at a dose of 15 ppm, the neonate had severe respiratory acidosis and was placed on extracorporeal membrane oxygenation (ECMO) for 2 days. On day 7 of life, surgical repair of the CDH was performed. After the intervention, iNO (20 ppm) had to be restarted because of severe pulmonary hypertension (PHT). Ventilatory support and iNO then were weaned progressively. However, each daily attempt to discontinue iNO (from 2 ppm to 0 ppm), led to severe desaturation with significant right-to-left shunting. At the age of 33 days, dipyridamole (persantin) was administered intravenously at a dose of 0,4 mg/kg/min over 10 minutes and repeated every 12 hours for a total of 3 doses. After the second administration of dipyridamole, iNO could be stopped without rebound of PHT, and the neonate was extubated 1 week later. The authors report the use of dipyridamole for successful withdrawal of iNO. By inhibition of phosphodiesterase type 5, dipyridamole has the potential to increase the level of cyclic guanosine monophosphate in vascular smooth muscle cells, permitting vasodilation and restoration of endogenous NO. J Pediatr Surg 36:1864-1865.
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PMID:The use of dipyridamole to wean from inhaled nitric oxide in congenital diaphragmatic hernia. 1173 27

Nitric oxide (NO) plays a major role in the modulation of perinatal pulmonary vascular tone. Congenital diaphragmatic hernia (CDH), a major cause of severe persistent pulmonary hypertension of the newborn (PPHN), is often refractory to inhaled NO. Alterations in NO/cyclic guanosine 3',5' monophosphate (cGMP)-mediated pulmonary vasodilatation may contribute to PPHN in CDH. We assessed NO/cGMP-mediated pulmonary vasorelaxation in vitro in 140-d gestational lamb fetuses with surgically created left CDH (term = 147 d) to age-matched controls. Relaxation of fourth generation intralobar pulmonary artery rings in response to the endothelium-dependent vasodilator, acetylcholine (ACh), and to the specific inhibitor of cGMP-phosphodiesterase (PDE), zaprinast, did not differ between the two groups. By contrast, relaxation in response to the calcium ionophore A23187 was impaired in CDH as compared with control animals. Relaxation in response to the NO donor sodium nitroprusside (SNP) (a direct activator of soluble guanylyl cyclase [sGC]) was also impaired in CDH animals as compared with controls. Repeating the challenge increased vasorelaxation in response to SNP in CDH as compared with control animals. Immunohistochemistry revealed the presence of endothelial NO-synthase in the endothelium of pulmonary arteries from both control and CDH animals. We conclude that endothelium-dependent vasodilatation in response to ACh and A23187 was differently affected in the fetal surgical CDH-lamb model. Furthermore, activity of sGC but not that of PDE was impaired in CDH animals. PPHN and decreased inhaled NO responsiveness in CDH may involve decreased sGC activity.
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PMID:Altered guanylyl-cyclase activity in vitro of pulmonary arteries from fetal lambs with congenital diaphragmatic hernia. 1209 Dec 44

Persistent pulmonary hypertension is seen in association with a number of diseases and conditions in the newborn including perinatal asphyxia, meconium aspiration syndrome, Group B strep sepsis, and certain surgical conditions such as congenital diaphragmatic hernia. The conventional therapy of persistent pulmonary hypertension is discussed as well as the adjunctive role of surfactant replacement therapy and high frequency ventilation. The mechanism of action of inhaled nitric oxide as a selective pulmonary vasodilator is explained. Human neonatal clinical experience is chronicled from the original studies of Roberts in 1992 and Kinsella in 1993. A review of three large prospective randomized trials of nitric oxide is presented as well as a summary of new areas of investigation including the use of nitric oxide in pre-term infants and the use of nitric oxide in the prevention of chronic lung disease. Current dosing recommendations are presented as well as guidelines recently published from the American Academy of Pediatrics. A review of follow up literature in relationship to patients receiving inhaled nitric oxide is also summarized.
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PMID:Status report: inhaled nitric oxide in persistent pulmonary hypertension/hypoxic respiratory failure of neonate. 1210 54

Congenital diaphragmatic hernia occurs in approximately 1 in every 2500 live births and is associated with a reported mortality of almost 35% in live-born patients and a higher mortality when in utero deaths are counted. Ventilator-induced lung injury, pulmonary hypoplasia, and other associated anomalies account for the high death rate. Numerous adjunctive measures have been used to treat these patients. Inhaled vasodilators (nitric oxide), intravenous vasodilators, and fetal therapy have no proven benefit. While animal models of congenital diaphragmatic hernia are surfactant deficient, controversy remains over the use of surfactant in infants. There has been no clinical trial showing any clear benefit with the use of exogenous surfactant in these patients. Similarly, prenatal corticosteroids show some improvements in animal models, but again, there is a complete absence of supportive data to show benefit in humans. Mechanical ventilator strategies that limit ventilator-induced lung injury by avoiding hyperventilation and lung over inflation are the strategies currently in use that have been associated with improved survival. Long-term follow-up of these patients is quite important since gastroesophageal reflux, developmental delay, chronic lung disease, and chest wall deformity are all seen with increased frequency in these children.
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PMID:Congenital diaphragmatic hernia. 1213 Sep 16

Management of congenital diaphragmatic hernia has changed dramatically over the past couple of decades. Until the early 1980s, it was felt that the abdominal contents should be returned to the abdomen as soon as possible to allow the lungs to expand. It is now known that it is not the defect that causes respiratory distress, but the infant's hypoplastic lungs and accompanying pulmonary hypertension. Advances in treatment and technology have contributed to changes in management. Ultrasonography now allows for early prenatal detection. Prenatal treatment modalities include in utero tracheal ligation and maternal antenatal steroids. Postnatal modalities have expanded to include permissive hypercapnia, high-frequency ventilation, inhaled nitric oxide, pharmacologic support, exogenous surfactant, and extracorporeal membrane oxygenation. Liquid ventilation and lobar lung transplantation have also been tried. In spite of these advances, the overall survival rate remains about 63 percent.
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PMID:Current and emerging treatment for congenital diaphragmatic hernia. 1214 12

Nitric oxide (NO) inhalation therapy relaxes preconstricted pulmonary blood vessels without causing concomitant systemic hypotension and increases oxygen uptake into the blood. NO inhalation is a new treatment for various disorders of neonates (respiratory distress syndrome, persistent pulmonary hypertension, congenital heart disease and congenital diaphragmatic hernia). There is no references of its use in congenital cystic adenomatoid malformation (CCAM). We report a case of a newborn of 33 week's gestation. The infant underwent resection of the CCAM that had occupied the right middle lobe. At the end of the operation, arterial blood gases at a fractional inspired oxygen concentration (FiO2) of 1.0 reveled acidosis and severe hypoxemia probably due to persistent pulmonary hypertension. NO therapy was used for 16 hours with decreased oxygen need and increase of arterial blood oxygen data. According to the extent of the adenomatoid lesion, likely due to the compression of the surrounding tissue, these patients at times postoperatively develop difficulty in oxygenation and ventilation and the changes are similar to those patients with congenital diaphragmatic hernia. The use of NO in these disorders are successfull.
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PMID:[Use of nitric oxide in a newborn child with pulmonary cystic adenomatoid malformation]. 1260 21

To date, uniform standards for congenital diaphragmatic hernia (CDH) management have not existed. The purpose of this study was to evaluate the evolving clinical outcome of the patients with CDH and to present our recent management protocol using echocardiography. Sixty patients treated for CDH at our hospital from 1978 through 2001 were reviewed. Periods of treatments were divided arbitrarily into three periods;1978-1991 (period I, n=26), 1992-1994 (period II, n=6), 1995-2001 (period III, n=28). Immediate repair was performed during period I. We performed preoperative stabilization and delayed repair since the start of period II, and nitric oxide (NO) was introduced in period III. In period III, our management strategy was the use of fentanyl for sedation and analgesia; vasoactive agents such as dopamine, dobutamine, and prostaglandin E1 in selected cases; the use of high-frequency oscillating ventilation (HFOV), inhaled NO; and venovenous extracorporeal membrane oxygenation (ECMO) if indicated. The details of stabilization management and the timing of surgery were determined using echocardiography to evaluate pulmonary hypertension (PH) by measuring dimension and shunt patterns through the ductus arteriosus (DA), right pulmonary artery (rPA) and left pulmonary artery (lPA). Overall, 42 of 60 patients survived (70%). The number of patients surviving in each period was 14 of 26 (54%) in period I, 4 of 6 (67%) in period II, and 24 of 28 (86%) in period III. Seventeen of 28 patients in period III required inhaled NO (group A). Of these 17 patients, 5 required ECMO; of these 5, 3 were long-term survivors. The remaining 11 patients from period III who were managed without NO (group B) survived. In left-sided CDH cases, the dimension of DA at admission in group A (5.07+/-1.79 mm) was significantly larger than in group B (2.99+/-1.68 mm) (P<0.01). The dimension of rPA in group A (3.37+/-0.80 mm) was significantly smaller as compared with group B (4.28+/-0.72 mm) (P<0.01). Although the dimension of lPA was not significantly different between group A (3.03+/-0.74 mm) and group B (3.46+/-0.48 mm), lPA blood flow was noticeably stronger in group B. DA shunt patterns were bi-directional (53%), right-to-left (40%) and left-to-right (7%) in group A, whereas no patients in group B showed a right-to-left shunt pattern. After confirmation of closure of DA or dominant left-to-right shunt, and marked increase of pulmonary arterial blood flow, patients in both group A and B underwent surgery successfully. In four non-survivors, findings of improving PH were not observed. We conclude that echocardiographic examination is useful to manage persistent pulmonary hypertension with recent treatment modalities including NO and HFOV and to determine the proper timing of surgery, which contributes to an improved outcome of CDH.
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PMID:Congenital diaphragmatic hernia: efficacy of ultrasound examination in its management. 1268 43

Neonates with congenital diaphragmatic hernia (CDH) suffer from a diaphragmatic defect, lung hypoplasia, and pulmonary hypertension, with poor lung function forming the major clinical challenge. Despite prenatal diagnosis and advanced postnatal treatment strategies, the mortality rate of CDH is still high. CDH has been subject of extensive research over the past decades, but its etiology remains unknown. A major problem with CDH is the failure to predict the individual response to treatment modalities like high-frequency ventilation, inhaled nitric oxide, and extracorporeal membrane oxygenation. In this study, we tested the possibility that CDH lungs are surfactant protein deficient, which could explain the respiratory failure and difficulties in treating CDH infants. We investigated this hypothesis in the nitrofen-induced CDH rat model and assessed the cellular concentrations of surfactant protein (SP)-A, -B, and -C mRNA with a quantitative radioactive in situ hybridization technique. No differences were observed between control and CDH lungs for SP mRNA expression patterns. The cellular concentration (mean OD) of SP-A and SP-B mRNA was similar at all stages whereas the mean OD of SP-C mRNA and the volume fraction of cells (% Area) expressing SP mRNA was higher in CDH lungs at term. Immunohistochemical analysis revealed no differences between control and CDH lungs for SP protein expression. No differences in the mean OD or % Area for the SP mRNAs were found between the ipsi- and contralateral side of CDH lungs. We conclude that there is no primary deficiency of surfactant proteins in the nitrofen-induced CDH rat model.
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PMID:Pulmonary surfactant protein A, B, and C mRNA and protein expression in the nitrofen-induced congenital diaphragmatic hernia rat model. 1290 92

Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.
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PMID:Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. 1498 Feb 86

Extracorporeal membrane oxygenation (ECMO) consists of the application of intermediate-term cardiopulmonary bypass for the treatment of potentially reversible heart and/or lung failure in the neonate, child, and adult. Applications in the neonate include congenital diaphragmatic hernia, pulmonary hypertension, meconium aspiration syndrome, and pre- and post-operative congenital heart surgery support. In the older child, myocarditis, infections, and respiratory failure (RSV and ARDS) are the most frequent indications, in addition to peri-operative cardiac surgical support. A review of the institutional experiences at the University of Louisville spanning a 15-year period and comparison international data will be presented, along with a pertinent review of the literature. Technical considerations, complications, and long-term outcomes will be reviewed, and the potential interface between ECMO and other, less invasive technologies, i.e., high-frequency ventilation, replacement surfactant, and nitric oxide, will be discussed.
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PMID:Update on extracorporeal membrane oxygenation. 1498 Feb 91


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