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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to assess the role of nitric oxide (NO) and endothelin (ET)-1 in the pathophysiology of persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created congenital diaphragmatic hernia (CDH). The pulmonary vascular response to various agonists and antagonists was assessed in vivo between 128 and 132 days gestation. Age-matched fetal lambs served as control animals. Control and CDH lambs had similar pulmonary vasodilator responses to acetylcholine, sodium nitroprusside, zaprinast, and dipyridamole. The ET(A)-receptor antagonist BQ-123 caused a significantly greater pulmonary vasodilatation in CDH than in control animals. The ET(B)-receptor agonist sarafotoxin 6c induced a biphasic response, with a sustained pulmonary vasoconstriction after a transient pulmonary vasodilatation that was not seen in CDH animals. We conclude that the NO signaling pathway in vivo is intact in experimental CDH. In contrast, ET(A)-receptor blockade and ET(B)-receptor stimulation significantly differed in CDH animals compared with control animals. Imbalance of ET-1-receptor activation favoring pulmonary vasoconstriction rather than altered NO-mediated pulmonary vasodilatation is likely to account for persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created CDH.
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PMID:ET(A)-receptor blockade and ET(B)-receptor stimulation in experimental congenital diaphragmatic hernia. 1078 22

Over the last two decades there has been a constant improvement in the understanding of the pathophysiology of Congenital Diaphragmatic Hernia (CDH) and its management. However, the ideal treatment remains elusive. The earlier management strategy of immediate surgery is replaced by the principle of physiological stabilisation and delayed surgery. Conventional mechanical ventilatory techniques, with high pressures and hyperventilation to reverse ductal shunting and cause alkalinization, are being questioned because of the risks of barotrauma and consequent broncho-pulmonary dysplasia. It has also been shown that paralysis with pancuronium bromide for patients on conventional mechanical ventilation results in increased incidence of sensorineural hearing loss in childhood survivors of CDH. With the introduction of the concept of permissive hypercapnia and high frequency oscillation ventilation, the complications of pulmonary barotrauma are circumvented. Although ECMO therapy is invasive, yet has improved survival by about 15% independently, especially in critically ill infants who have the predictive mortality rate of more than 80%. Further insights into the pathophysiology of CDH and the introduction of less invasive therapeutic techniques in the form of high frequency oscillation ventilation, inhalation nitric oxide, surfactant, and perfluorocarbon liquid ventilation may even make the need for ECMO redundant.
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PMID:Congenital diaphragmatic hernia. 1102 21

Pulmonary hypertension of the newborn is an important cause of hypoxaemia, particularly in the at term or near term neonate. It can occur as a primary condition or secondary to a variety of other diseases. Endogenous nitric oxide is an important modulator of vascular tone in pulmonary circulation. Initial uncontrolled studies indicated that inhalation of nitric oxide resulted in a reduction in pulmonary hypertension, with improvement in oxygenation, but no change in the systemic vascular resistance. There have now been a number of randomised trials performed exploring the efficacy of inhaled nitric oxide. These trials have demonstrated that in at term or near term infants, inhaled nitric oxide reduces the combined end point of death or the need for extracorporeal membrane oxygenation. The significant effect seems due to the reduced extracorporeal membrane oxygenation requirement. No such beneficial effect has been consistently reported in infants with congenital diaphragmatic hernia. Randomised trials have failed to highlight long-term positive results in preterm infants. Inhaled nitric oxide has side effects, although those due to nitrogen dioxide and methaemoglobin formation can be minimised by appropriate nitric oxide delivery. It is important to use the smallest effective nitric oxide dose, continuous nitric oxide and nitrogen dioxide monitoring and frequent methaemoglobin analyses. Careful patient selection should be undertaken, avoiding those at high risk of haemorrhagic complications. Longer term follow-up studies are required to determine the real risk:benefit ratio of inhaled nitric oxide treatment.
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PMID:Inhaled nitric oxide in the neonatal period. 1106 Jul 64

We have investigated the effects of high arginine (Arg) levels (7.5 mg/100 g body weight per hour) on the early integration of biocompatible mesh grafts into the rat abdominal wall. Studies were performed over implantation intervals of 6, 12, 24 or 48 hours (n=12, each). Arginine and related compounds were quantified in plasma, wound fluids and multiple tissues. Plasma nitric oxide (NO) production was studied. Strips were taken from the polypropylene fiber-host tissue interfaces (PTIs) for optical microscopic analysis and for immunohistochemical analysis using rat-specific antibodies against type I and type III collagens. Exogenous Arg was metabolized at the peripheral tissues but reliably reached the wound space. High amounts of Arg and ornithine (Orn) were detected in the specimens considered. No changes on citrulline (Ctr) or NO concentrations were observed, overall suggesting that, during the period studied, the arginase pathway predominated. The acute scarring response differed significantly in the two placements considered. The P-SS interface evidenced more extensive new tissue growth than the P-DS interface. Forty-eight hours after mesh implantation cellular infiltration, fibroblast proliferation, and mesh-surrounding angiogenesis were higher in the arginine-treated rats. Type III collagen staining was related to arginine treatment, being higher (++) in the study group. In conclusion, and independently of the site of mesh placement, supplemental Arg seemed to favorably affect early local collagen deposition. This could be potentially helpful to ameliorate the integration of biomaterials into the tissues and, consequently, to allow for the design of more selective therapeutic strategies to prevent hernia recurrence rates.
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PMID:Early effects of exogenous arginine after the implantation of prosthetic material into the rat abdominal wall. 1106 72

Inhaled nitric oxide (iNO) has emerged as a promising therapeutic agent in the treatment of persistent pulmonary hypertension of the newborn. Several theories exist regarding causes of both response and nonresponse to iNO. Clinical trials differentiate disease entities (primary vs secondary persistent pulmonary hypertension associated with meconium aspiration syndrome, pneumonia or congenital diaphragmatic hernia) and their specific response rates. iNO combined with high-frequency ventilation appears to be superior to inhalation of nitric oxide (NO) during conventional ventilation. Little is known regarding the role of the degree of lung expansion and its modification -- no matter what mode of ventilation is applied. Gestational age plays an important role in relation to the potential adverse effects of NO. Of particular concern in the premature neonate is the effect of NO on bleeding time and the inhibition of platelet aggregation. Those potentially hazardous effects need to be carefully weighed against early intervention with iNO at a comparably low oxygenation index in order to prevent the vicious cycle of hypoxaemia and subsequent increased right-to-left shunting. Further studies are required to determine the optimal timing, mode of delivery and mode of ventilation used with iNO therapy in order to optimise the response of premature and term neonates.
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PMID:Response to inhaled nitric oxide in premature and term neonates. 1121 69

This study documents how congenital diaphragmatic hernia (CDH) is managed in level III neonatal intensive care units (NICUs) in western Canada and examines perinatal factors predictive of the need for extracorporeal membrane oxygenation (ECMO). Information was obtained retrospectively from all level III NICUs in western Canada about the management of infants with CDH between 1992 and 1996; 91 infants with isolated CDH were identified. A prenatal diagnosis was made in 42 cases (46%). Surfactant was used in 53%, high-frequency oscillation (HFO) in 29%, and nitric oxide (NO) in 27%. Of the 69 infants born in referral centers, 29 (42%) were referred for possible ECMO; 17 (59%) of those required ECMO, with 65% survival. The overall requirement for ECMO was 30%. Death or ECMO occurred in 40% of cases overall. Overall survival was 82%. Survival in those needing ECMO was 74%, and in those not needing ECMO 86%. Significant predictors of death or ECMO were: prenatal diagnosis (P < 0.05), maximum postductal arterial partial pressure of oxygen (PaO2) < 100 mmHg (P < 0.001), and an oxygenation index (OI) at 6 h > 15 (P < 0.001). In cases where there is a prenatal diagnosis of CDH the mother should deliver at an ECMO center. Alternatively, an OI of > 15 at 6 h and PaO2 < 100 mmHg should prompt referral to an ECMO center.
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PMID:The western Canadian experience with congenital diaphragmatic hernia: perinatal factors predictive of extracorporeal membrane oxygenation and death. 1131 87

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.
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PMID:Pharmacologic therapy of persistent pulmonary hypertension of the newborn. 1131 14

Congenital Diaphragmatic Hernia (CDH) occurs in one of every 2000-3000 births, and most of them are sporadic, and therefore recognized as a circumstantial event. But its occurrence in 85 children among the 40 families is also reported, and some reports suggest that an autosomal recessive gene may be responsible for this disease. We experienced identical twins (babies A and B) both with prenatally diagnosed CDH. They were delivered by emergent cesarean section at 33 weeks of gestation with birth weight of 1857 g and 1561 g, respectively. They were intubated immediately after birth, and ventilated with high frequency oscillation. Baby A presented persistent pulmonary hypertension of newborn, and received nitric oxide inhalation. At the age of 2 days, both of them were stabilized and underwent repair of CDH. After the repair, baby A developed perforation of ileum, airway bleeding and retinopathy of prematurity (ROP), and needed 28 days before extubation. Baby B also developed ROP, but had no other problem, and the trachea was extubated at the age of 12 days. They are the seventh pair reported in the world literature.
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PMID:[Perioperative management of twins with prenatally diagnosed congenital diaphragmatic hernia]. 1134 53

Persistent pulmonary hypertension of the newborn (PPHN) is a cardiopulmonary disorder characterized by systemic arterial hypoxemia secondary to elevated pulmonary vascular resistance with resultant shunting of pulmonary blood flow to the systemic circulation. This disorder can be classified into four forms dependent on the etiology of the pulmonary hypertension: (1) Hypoplastic lung associated with congenital diaphragmatic hernia and oligohydramnions. (2) Primary PPHN (without known causative factor), such as preterm PPHN. (3) Secondary PPHN (with known causative factor), such as meconium aspiration syndrome, birth asphyxia or respiratory distress syndrome. (4) Relative PPHN associated with heart failure of hydrops fetalis or ischemic myocardial dysfunction. Inhalation of nitric oxide, which previously known as endothelial-derived-relaxation-factor, has been studied intensively as therapy for PPHN.
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PMID:[Persistent pulmonary hypertension of the newborn]. 1141 Nov 37

Inhaled nitric oxide (iNO) improves oxygenation in term and near-term infants with persistent pulmonary hypertension of the newborn (PPHN) and decreases the need for treatment with extracorporeal membrane oxygenation (ECMO). This mode of treatment is currently being introduced in Malaysia. We report our preliminary experience using low dose inhaled nitric oxide (20 parts per million) in three newborn infants (meconium aspiration syndrome, primary PPHN and congenital diaphragmatic hernia) with severe PPHN who fulfilled criteria for ECMO with a mean oxygenation index (OI) of 40. Two of the infants showed rapid and sustained improvement in oxygenation with a reduction in oxygenation index (OI) over 24 hours. The infant with diaphragmatic hernia showed an initial improvement in OI, which was unsustained and subsequently died. All three infants did not show significant elevation of methemoglobin or nitrogen dioxide (NO2). Inhaled nitric oxide is an effective and safe treatment for severe PPHN that can be used in a developing country like Malaysia.
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PMID:Low-dose inhaled nitric oxide in term and near-term infants with hypoxic respiratory failure: a Malaysian experience. 1173 80


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