Effects of megestrol acetate on weight gain, body composition, and pulmonary function in patients with cystic fibrosis.

Objectives: Malnutrition is a negative prognostic indicator in patients with cystic fibrosis (CF) and may accentuate pulmonary decline. We tested whether megestrol acetate would have beneficial effects on growth in patients with CF and pancreatic insufficiency.

Study Design: We performed a randomized, double-blind, placebo controlled study.

Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis.

Here we report the effects of gentamicin treatment on cystic fibrosis transmembrane regulator (CFTR) production and function in CF airway cells and patients with CF with premature stop mutations. Using immunocytochemical and functional [6-methoxy-N- (3-sulfopropyl) quinolinium (SPQ)-based] techniques, ex vivo exposure of airway cells from stop mutation CF patients led to the identification of surface-localized CFTR in a dose-dependent fashion. Next, five patients with CF with stop mutations and five CF control subjects were treated with parenteral gentamicin for 1 wk, and underwent repeated in vivo measures of CFTR function (nasal potential difference [PD] measurements and sweat chloride [Cl(-)] testing).

A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis.

Immunologic reactivity to lipid-DNA conjugates has traditionally been viewed as less of an issue than with viral vectors. We performed a dose escalation safety trial of aerosolized cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the lower airways of eight adult cystic fibrosis patients, and monitored expression by RT-PCR. The cDNA was complexed to a cationic lipid amphiphile (GL-67) consisting of a cholesterol anchor linked to a spermine head group.

Chronic aspiration in children: evaluation of the lipid-laden macrophage index.

Chronic pulmonary aspiration (CPA) causes significant morbidity, but is underdiagnosed because of difficulties in establishing a diagnosis. The lipid-laden macrophage index (LLMI) is said to differentiate between those with and without CPA. Records of 113 patients were reviewed to determine specificity and sensitivity of the LLMI for CPA.

Hemodynamic responses of chronically instrumented piglets to bolus injections of group B streptococci.

Group B beta-hemolytic Streptotocci cause pulmonary hypertension when injected into animals and may precipitate the persistent pulmonary hypertension syndrome in infected human neonates. We used chronically instrumented piglets to study the effects of repeated injections of heat-killed group B Streptococcus (GBS) type III. Daily exposure to GBS was associated with a 2-fold or greater potentiation of pulmonary and systemic hypertensive responses after 1 wk.

Thromboxane synthesis inhibition reverses group B Streptococcus-induced pulmonary hypertension.

Group B Streptococcus (GBS) sepsis in humans may cause the persistent pulmonary hypertension syndrome. Infusions of GBS in animals elevate pulmonary artery pressure (PAP) and resistance and are associated with elevated thromboxane levels. We investigated the hemodynamic effects of the specific thromboxane synthesis inhibitor, dazmegrel, in a piglet model of GBS-induced pulmonary hypertension.

Intrauterine herpes simplex virus infections.

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects.

Influence of prostaglandin D2 on hemodynamic effects of group B streptococcus in neonatal lambs.

Infusions of group B streptococci cause pulmonary hypertension in several neonatal animal models. A continuous infusion of prostaglandin D2 reduced the magnitude of this pulmonary hypertensive response; indomethacin completely blocked the response. Prostaglandin D2 or cyclooxygenase inhibitors may be important therapeutic agents for infants with group B streptococcal sepsis who manifest pulmonary hypertension.

Alkalosis attenuates hypoxic pulmonary vasoconstriction in neonatal lambs.

Hyperventilation (respiratory alkalosis) is an important treatment for persistent pulmonary hypertension in neonates. The precise way that hyperventilation attenuates hypoxic pulmonary vasoconstriction is unclear. We studied the effect of alkalosis on hypoxia-induced pulmonary vasoconstriction in 13 acutely instrumented, pentobarbital anesthetized, neonatal lambs.

Hemodynamic effects of nifedipine in normoxic and hypoxic newborn lambs.

We studied the effects of nifedipine, a calcium-channel blocker, in two acutely instrumented groups of newborn lambs during normoxic and hypoxic conditions. Nifedipine at 10 or more micrograms/kg reduced systemic, but not pulmonary artery pressure and resistance in normoxic lambs. When acute hypoxia was produced in these animals, 50 or more micrograms/kg reduced, but did not prevent, the expected rise in pulmonary pressure and resistance.

Prostaglandins, related compounds, and the perinatal pulmonary circulation.

It is clear that prostaglandins and related compounds are important in the physiology and pathophysiology of the perinatal pulmonary circulation. This article focuses on what is known about prostaglandin-related compounds (PRC) in the pulmonary circulation of the developing and newly born mammal. Also included is a discussion of the effects of PRC on the ductus arteriosus and on the systemic circulation.

Control of pulmonary vascular resistance in the fetus and newborn.

This article describes the anatomy and physiology of the fetal, transitional, and neonatal circulations and then reviews our current state of knowledge about the many factors that work in concert to govern pulmonary vascular resistance.

Prostaglandin D2 inhibits hypoxic pulmonary vasoconstriction in neonatal lambs.

Intrapulmonary injections of prostaglandin D2 (PGD2) reduce pulmonary arterial pressure and resistance in fetal and hypoxic neonatal lambs without affecting systemic arterial pressure. This apparently specific pulmonary effect of PGD2 could be explained by inactivation of the agent during passage through the pulmonary capillary bed. We therefore studied the effects of both pulmonary and systemic infusions of PGD2 on the acute vascular response to a 1-min episode of hypoxia in newborn lambs.

Effects of PEEP and tolazoline infusion on respiratory and inert gas exchange in experimental meconium aspiration.

Meconium aspiration syndrome often produces respiratory failure in the neonate. We utilized the multiple inert gas elimination technique to study the effects on respiratory and inert gas exchange of the application of positive end expiratory pressure or continuous infusion of tolazoline HCl. The application of PEEP, with the optimal level of PEEP defined for each animal, produced a decrease in AaDO2 and pulmonary shunt, without an increase in blood flow to low VA/Q areas, or an increase in dead space.

Adult respiratory distress syndrome in a pediatric intensive care unit: predisposing conditions, clinical course, and outcome.

Adult respiratory distress syndrome, commonly seen in adults, is not well recognized in children. A retrospective chart review was carried out to determine the relative incidence, predisposing conditions, clinical course, and outcome of children with adult respiratory distress syndrome. fifteen patients were identified.

Ventilation by high-frequency oscillation in rabbits with oleic acid lung disease.

The feasibility and efficiency of ventilation by high-frequency oscillation (HFO) were examined in animals with diffuse hemorrhagic lung disease. Twenty-four hours after injection with 0.12 ml/kg oleic acid, 11 spontaneously breathing rabbits had a mean (+/- SD) arterial O2 partial pressure (PaO2) of 65 +/- 16 Torr and arterial CO2 partial pressure (PaCO2) of 38 +/- 7 Torr [inspired fractional O2 concentration (FIO2) of 0.