Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure.

Objectives And Background: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria.

Study Design: A total of 108 children (median age 2.

In vivo evidence for a myogenic response in the fetal pulmonary circulation.

In vitro studies have suggested that pulmonary arteries can exhibit a myogenic response and that this myogenic response may be potent during the perinatal period. However, whether a myogenic response can be demonstrated to exist in vivo and the potential role of the myogenic response on the regulation of pulmonary blood flow during fetal life is unknown. We hypothesized that an acute increase in pulmonary artery pressure resulting from partial compression of the ductus arteriosus (DA) in the fetus may simultaneously activate two opposing responses: 1) blood flow-induced vasodilation (owing to shear stress); and 2) pressure-induced vasoconstriction (owing to the myogenic response).

Inducible NO synthase inhibition attenuates shear stress-induced pulmonary vasodilation in the ovine fetus.

Recent studies have suggested that type II (inducible) nitric oxide (NO) synthase (NOS II) is present in the fetal lung, but its physiological roles are uncertain. Whether NOS II activity contributes to the NO-mediated fall in pulmonary vascular resistance (PVR) during shear stress-induced pulmonary vasodilation is unknown. We studied the hemodynamic effects of two selective NOS II antagonists [aminoguanidine (AG) and S-ethylisothiourea (EIT)], a nonselective NOS antagonist [nitro-L-arginine (L-NNA)], and a nonselective vasoconstrictor (U-46619) on PVR during partial compression of the ductus arteriosus (DA) in 20 chronically prepared fetal lambs (mean age 132 +/- 2 days, term 147 days).

Smoking increases facial skin flap complications.

This study was undertaken to determine whether smokers have a higher risk of complications after reconstruction of facial skin defects. Ninety-one patients with facial skin defects reconstructed with local flaps were reviewed retrospectively. Thirty-eight (42%) were active smokers, 12 (13%) had not smoked for at least 1 year prior to surgery, and the rest were nonsmokers.

K+-channel blockade inhibits shear stress-induced pulmonary vasodilation in the ovine fetus.

To determine whether K+-channel activation mediates shear stress-induced pulmonary vasodilation in the fetus, we studied the hemodynamic effects of K+-channel blockers on basal pulmonary vascular resistance and on the pulmonary vascular response to partial compression of the ductus arteriosus (DA) in chronically prepared late-gestation fetal lambs (128-132 days gestation). Study drugs included tetraethylammonium (TEA; Ca2+-dependent K+-channel blocker), glibenclamide (Glib; ATP-dependent K+-channel blocker), charybdotoxin (CTX; preferential high-conductance Ca2+-dependent K+-channel blocker), apamin (Apa; low-conductance Ca2+-dependent K+-channel blocker), and 4-aminopyridine (4-AP; voltage-dependent K+-channel blocker). Catheters were inserted in the left pulmonary artery (LPA) for selective drug infusion and in the main pulmonary artery, aorta, and left atrium to measure pressure.

Influence of timing of morphine administration on postoperative pain and analgesic consumption.

We have investigated if a pre-emptive dose of morphine, given 30 min before skin incision, influenced postoperative pain and morphine consumption after hysterectomy. In a prospective, randomized, double-blind, placebo-controlled clinical study, patients received morphine 0.3 mg kg-1 at induction of anaesthesia or 30 min later at skin incision.

Effects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension.

Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation by increasing pulmonary vascular levels of cyclic guanosine monophosphate (cGMP). Dipyridamole, a drug with several putative vasodilator mechanisms, is an inhibitor of cGMP-specific phosphodiesterases (PDE5); it therefore has the potential to increase pulmonary vascular cGMP levels, lower pulmonary vascular resistance, augment iNO-induced pulmonary vasodilation, and attenuate excessive pulmonary vasoreactivity. To test dipyridamole in the pulmonary circulation, we studied pediatric patients undergoing cardiac catheterization who had severe resting pulmonary hypertension (Group 1; n = 11) or exaggerated acute hypoxia-induced pulmonary vasoconstriction (Group 2; n = 4).

Gongylonema macrogubernaculum in captive African squirrels (Funisciurus substriatus and Xerus erythropus) and lion-tailed macaques (Macaca silenus).

Necropsies performed between 1989 and 1995 on 15 African rope squirrels (Funisciurus substriatus) and 20 African ground squirrels (Xerus erythropus) from the Baltimore Zoo revealed 13 cases of gongylonemiasis. Nematodes were embedded in the epithelium of the esophagus, pharynx, buccal mucosa, and tongue, resulting in varying degrees of esophagitis, pharyngitis, stomatitis, and glossitis, respectively. Routine fecal examinations were negative, and the nematodes appeared to be unaffected by repeated treatments with ivermectin.

Acute hemodynamic effects of pulsed delivery of low flow nasal nitric oxide in children with pulmonary hypertension.

We studied 8 children, ages 8 months to 14 years, during cardiac catheterization in order to determine the acute hemodynamic effects of pulsed nasal cannula delivery of nitric oxide (NO) in children with pulmonary hypertension. NO was administered by continuous mask or pulsed nasal cannula in random order. All patients effectively triggered the NO pulsing device.

Inhaled nitric oxide therapy for pulmonary disease in pediatrics.

Inhaled nitric oxide (iNO) therapy improves gas exchange and lowers pulmonary vascular resistance in neonates and children with diverse cardiac and pulmonary disorders. Recent multicenter studies have shown that iNO reduces the need for rescue therapy with extracorporeal membrane oxygenation in term neonates with severe hypoxemic respiratory failure. In neonates with severe lung disease, responsiveness to iNO therapy can be enhanced by therapies which enhance lung recruitment, especially high-frequency oscillatory ventilation.

Endothelin A receptor blockade decreases pulmonary vascular resistance in premature lambs with hyaline membrane disease.

Endothelin (ET)-1 is a potent vasoconstrictor peptide that modulates basal pulmonary vascular resistance (PVR) in the normal ovine fetus and contributes to high PVR after chronic intrauterine pulmonary hypertension. Although high PVR is present in premature lambs with severe hyaline membrane disease (HMD), whether ET-1 plays a role in the pathophysiology of experimental HMD is unknown. To test the hypothesis that ET-1 activity contributes to high PVR in the premature lamb with HMD, we studied the hemodynamic effects of a selective ET(A) receptor antagonist, BQ 123, in 10 animals (gestational age 125 d; 147 d=term).

Anti-B4-blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma.

This phase II trial was undertaken to determine the toxicities, response rate, pharmacokinetics and frequency of human anti-mouse antibody (HAMA) and anti-ricin antibody (HARA) when the B-cell restricted immunotoxin anti-B4-bR was administered to patients with previously treated multiple myeloma (MM). Five patients with MM were scheduled to receive a 7 d continuous infusion of anti-B4-bR. The initial four patients received therapy at 40 microg/kg lean body weight (LBW)/d.

Response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn: relationship to baseline oxygenation.

Objective: We hypothesized that the magnitude of response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn would correlate with the degree of baseline hypoxemia.

Study Design: We performed a retrospective chart review of 15 consecutive newborn infants with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide as part of a pilot study. Oxygenation index was calculated for each patient at baseline and 0.

Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles.

Kv2.2, homologous to the shab family of Drosophila voltage-gated K+ channels, was isolated from human and canine colonic circular smooth muscle-derived mRNA. Northern hybridization analysis performed on RNA prepared from tissues and RT-PCR performed on RNA isolated from dispersed and selected smooth muscle cells demonstrate that Kv2.

Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease.

Objective: Inhaled nitric oxide therapy causes selective and sustained pulmonary vasodilation in patients with pulmonary hypertension; however, attempts to discontinue inhaled nitric oxide therapy may be complicated by abrupt life-threatening events. Dipyridamole, a cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, blocks the hydrolysis of cyclic guanosine monophosphate in vascular smooth muscle cells.

Methods: We studied 23 consecutive children who were treated with inhaled nitric oxide because of clinically significant pulmonary hypertension after surgery for congenital heart disease.

Dipyridamole potentiates pulmonary vasodilation induced by acetylcholine and nitric oxide in the ovine fetus.

Nitric oxide (NO) modulates pulmonary vascular resistance (PVR) in the normal fetus by increasing the cyclic guanosine 3',5'-monophosphate (cGMP) content of pulmonary vascular smooth muscle cells. Although several vasodilator stimuli, including acetylcholine, decrease fetal PVR through the release of endogenous NO, fetal pulmonary vasodilation is often transient despite prolonged treatment. Because cGMP is hydrolyzed and inactivated by cGMP-specific (type 5) phosphodiesterases (PDE5), we hypothesized that PDE5 activity contributes to high fetal PVR and limits the capability of the fetal pulmonary circulation to dilate or sustain vasodilation in response to cGMP-dependent stimuli.

Controversies in the use of inhaled nitric oxide therapy in the newborn.

Inhaled nitric oxide (NO) causes sustained improvement in oxygenation in near-term and term newborns with persistent pulmonary hypertension of the newborn (PPHN), and reduces the need for extracorporeal membrane oxygenation (ECMO). However, many questions remain concerning the application of inhaled NO to less severely ill infants, its use in units without immediate access to adjuvant therapies for hypoxemic respiratory failure, and in centers without ECMO. Particular vigilance must be given to the potential impact of widespread dissemination on inhaled NO therapy on time ECMO initiation, and the inappropriate use of inhaled NO in premature neonates.

Direct supervision: adding computer-assisted feedback and data capture to live supervision.

This is a critical review of live supervision with emphasis on technical innovations such as earphones or bug-in-the-ear, Teleprompters, and computers. A computer-assisted approach is described that overcomes many criticisms of live supervision. Direct supervision uses a computer monitor to unobtrusively provide information to the therapist about the supervisor's perceptions of the clients' and therapist's behavior, the expected therapeutic behaviors, and the therapist's "on target" behavior.

Inhaled nitric oxide and high frequency oscillatory ventilation in persistent pulmonary hypertension of the newborn.

Unlabelled: Inhaled nitric oxide (iNO) improves oxygenation in near-term and term newborns with persistent pulmonary hypertension of the newborn (PPHN), and decreases the need for treatment with extracorporeal membrane oxygenation. However, some patients with PPHN either do not respond or have only transient improvements in oxygenation during iNO therapy. Extrapulmonary shunting associated with high pulmonary vascular resistance in PPHN can cause critical hypoxaemia; however, the syndrome of PPHN is often associated with severe parenchymal lung disease (e.

Role of inducible nitric oxide synthase in regulation of pulmonary vascular tone in the late gestation ovine fetus.

Nitric oxide (NO) produced by NO synthase (NOS) modulates fetal pulmonary vascular tone and contributes to the fall in pulmonary vascular resistance (PVR) at birth. Although the inducible (type II) NOS isoform is present in human and rat fetal lungs, it is uncertain whether type II NOS activity contributes to vascular NO production in the fetal lung. To determine whether type II NOS is present in the ovine fetal lung and to study the potential contribution of type II NOS on the regulation of basal PVR in the fetus, we measured the hemodynamic effects of three selective type II NOS antagonists: aminoguanidine (AG), 2-amino-5,6-dihydro-6-methyl-4H-1,3 thiazine (AMT), and S-ethylisothiourea (EIT).

Impact of new treatments for neonatal pulmonary hypertension on extracorporeal membrane oxygenation use and outcome.

Objective: To determine the impact of new treatment modalities, including high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (INO), on extracorporeal membrane oxygenation (ECMO) use and outcome of neonatal patients with persistent pulmonary hypertension of the newborn.

Study Design: We reviewed the medical records of neonatal patients meeting established ECMO criteria from 1988 to 1995. Clinical data were gathered from this retrospective chart review.