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Biomedical subjects

Rita M Ryan

Publications and source records attributed to Rita M Ryan.

15 recordsLinked to original sources
PubMed2006

Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation.

Prostacyclin (PGI(2)) stimulates adenyl cyclase to synthesize cAMP within the vascular smooth muscle resulting in vasodilatation. Milrinone inhibits cAMP clearance by phosphodiesterase type III. We studied the dose response of pulmonary and systemic hemodynamics to intratracheal (IT) PGI(2) in newborn lambs with pulmonary hypertension (PH) and whether intravenous milrinone potentiate these effects. IT-PGI(2) at varying doses was administered to lambs with PH induced by prenatal ductal ligation. IT-PGI(2) doses were repeated in the presence of intravenous milrinone (bolus-100 microg/kg followed by infusion at 1 microg/kg/min). Increasing doses of IT-PGI(2) significantly decreased mean pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) and increased pulmonary blood flow (PBF). Intravenous milrinone by itself produced a significant reduction in PVR and a significant increase in PBF. Intravenous milrinone significantly shortened the onset, prolonged the duration and degree of pulmonary vasodilation produced by PGI(2). We conclude that intravenous milrinone potentiates the pulmonary vasodilator effects of PGI(2) at lower doses.

Animals↗
PubMed2006

Adjacent bronchus attenuates pulmonary arterial contractility.

Bronchus-derived relaxing factor (BrDRF) decreases contractility of newborn rat pulmonary arteries (PA) and is dependent on nitric oxide (NO) synthesis. In vivo, this factor appears to gain access via the adventitial side of the PA. However, the adventitia has been reported to be a barrier to NO. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine in nine juvenile lambs in the presence and absence of inhibitors of the NO pathway (LNA, ODQ, and Rp-8-Br-PET-cGMPS), cytochrome P-450 inhibitor (17-ODYA), perivascular nerve activity blocker (TTX), and superoxide scavenger (tiron), and following disruption of bronchial epithelium. We also evaluated whether BrDRF was effective on both the endothelial and/or adventitial side of PA. Fifth-generation PA rings with and without an attached bronchus were contracted in standard baths with norepinephrine. PA were dissected, cut open, and placed in a sided chamber in which adventitial and endothelial sides of the PA were exposed to unattached bronchus separately. Norepinephrine (10(-8) to 10(-5) M) contractions were expressed as a fraction of maximal KCl (118 mM) contractions. Norepinephrine contractions were significantly reduced by the presence of an attached bronchus, an effect reversed by pretreatment with LNA, ODQ, and Rp-8-Br-PET-cGMPS, and removal of bronchial epithelium. Unattached bronchus in the bath perfusing the adventitial side was effective in inhibiting the contractile response in PA. NO gas relaxed PA when administered on the endothelial side only. We speculate that BrDRF is a diffusible factor that crosses the adventitia and stimulates production of NO within the PA.

Animals↗
PubMed2006

Ovine bronchial-derived relaxing factor: changes with development and hyperoxic ventilation.

Recent studies suggest that a bronchial-derived relaxing factor (BrDRF) decreases the contractility of newborn, but not fetal, rat pulmonary arteries (PAs) by a nitric oxide (NO)-mediated mechanism. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine (NE) in late-gestation fetal (n = 7), neonatal (1 day old, n = 9), ventilated neonatal (24-h ventilation from birth with 100% oxygen, n = 9), and adult sheep (n = 6) in the presence and absence of the NO synthase inhibitor N(omega)-nitro-l-arginine (l-NNA). The sheep were anesthetized and killed, and fifth-generation PA rings with and without an attached adjacent bronchus (PA+Br) were contracted in standard tissue baths with NE (10(-8)-10(-6) M). NE contractions were expressed as fraction of KCl (118 mM) contraction and as grams of contraction force. NE contractions were significantly diminished by the presence of an attached bronchus in the neonatal and ventilated neonatal and adult, but not fetal, lambs. Hyperoxic ventilation markedly increased NE contractions in PA and PA+Br. l-NNA significantly enhanced NE contractions in PA+Br in postnatal but not in fetal lambs. Pretreatment with l-NNA abolished the difference between NE contractions in PA and PA+Br in neonatal but not in hyperoxic ventilated neonatal lambs. We conclude that there is a BrDRF that is developmentally regulated and has vascular activity postnatally but not during fetal life. The effect of BrDRF is predominantly mediated by NO in air-breathing neonatal lambs but may involve a second non-NO mediator following hyperoxic ventilation. We speculate that BrDRF may have an important role in postnatal changes in pulmonary arterial reactivity.

Aging↗
PubMed2006

C-type natriuretic peptide and its receptor are downregulated in pulmonary epithelium following birth.

C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family and acts through the membrane bound guanylyl cyclase linked natriuretic peptide receptor B (NPR-B) to increase intracellular cGMP. Activation of the CNP/NPR-B pathway in pulmonary epithelium has been linked to the inhibition of amiloride-sensitive sodium absorption and to the stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR). Given the importance of ion movement across the pulmonary epithelium of the fetal and newborn lung, we sought to examine the expression of CNP and NPR-B in pulmonary epithelium of the developing fetal lamb and following the transition to air breathing. Lambs were sacrificed at 100 and 136 days of gestation and at 3 days, and 4 weeks after full term delivery. Lung sections were immunostained for CNP and NPR-B. At 100 days of gestation, staining for CNP and NPR-B was absent within all pulmonary epithelium. At 136 days of gestation, prominent staining for both CNP and NPR-B was seen within alveolar type II cells, non-ciliated cells of the distal airways (Clara cells), and ciliated epithelium of the upper airways. At both 3 days and 4 weeks following birth, staining for CNP and NPR-B was absent in alveolar type II cells, ciliated bronchial epithelium and was markedly reduced in Clara cells. The presence of CNP and NPR-B within the pulmonary epithelium in the nearterm fetal period and its rapid downregulation following birth suggests that CNP may contribute to the maintenance of the fluid-filled lung through the regulation of trans-epithelial ion flux.

Animals↗
PubMed2005

Pulmonary arterial contractility in neonatal lambs increases with 100% oxygen resuscitation.

The optimal Fi(O2) during neonatal resuscitation is a subject of controversy. The effect of exposure to high levels of inspired oxygen on pulmonary arterial (PA) contractility is not known. We studied differences in PA vasoreactivity in term lambs initially ventilated with 21% or 100% oxygen, followed by continued ventilation using oxygen as needed for 24 h, or ventilated with 100% oxygen for 24 h and room air breathing 1-d-old lambs. Term lambs were delivered by cesarean section, intubated, and ventilated with 21% (21%Res) or 100% oxygen (100%Res) for the first 30 min of life. Subsequently, the ventilator Fi(O2) was adjusted to maintain a Pa(O2) between 45 and 65 mm Hg for 24 h. Five lambs were ventilated continuously with 100% oxygen (100%24h). Six spontaneously breathing newborn lambs (RA Spont) were studied for comparison. Lambs were killed at 24 h of life and PA rings were isolated and contracted with norepinephrine (NE) and KCl and some were relaxed with A23187 and SNAP in tissue baths. NE and KCl induced contractions were highest in PA isolated from 100%24h lambs, and were significantly higher in 100%Res lambs than PA from 21%Res lambs. Contraction responses in PA from RA Spont lambs were similar to 21%Res lambs. Relaxations to A23187 and SNAP were similar among all ventilated groups. PA contractility to NE and KCl is increased following both brief (30 min) and prolonged (24 h) exposure to 100% oxygen during mechanical ventilation. In contrast, normoxic resuscitation and ventilation do not increase PA contractility.

Animals↗
PubMed2005

Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low-birth-weight infants: a randomized controlled trial.

OBJECTIVE: To test the hypothesis that pressure-regulated volume control (PRVC), an assist/control mode of ventilation, would increase the proportion of very low-birth-weight infants who were alive and extubated at 14 days of age as compared with synchronized intermittent mandatory ventilation (SIMV). STUDY DESIGN: Ventilated infants with birth weight of 500 to 1249 g were randomized at less than 6 hours of age either to pressure-limited SIMV or to PRVC on the Servo 300 ventilator (Siemens Electromedical Group, Danvers, Mass). Infants received their assigned mode of ventilation until extubation, death, or meeting predetermined failure criteria. RESULTS: Mean +/- SD birth weights were similar in the SIMV (888 +/- 199 g, n = 108) and PRVC (884 +/- 203 g, n = 104) groups. No differences were detected between SIMV and PRVC groups in the proportion of infants alive and extubated at 14 days (41% vs 37%, respectively), length of mechanical ventilation in survivors (median, 24 days vs 33 days, respectively), or the proportion of infants alive without a supplemental oxygen requirement at 36 weeks' postmenstrual age (57% vs 63%, respectively). More infants receiving SIMV (33%) failed their assigned ventilator mode than did infants receiving PRVC (20%). Including failure as an adverse outcome did not alter the overall outcome (39% of infants in the SIMV group vs 35% of infants in the PRVC group were alive, extubated, and had not failed at 14 days). CONCLUSION: In mechanically ventilated infants with birth weights of 500 to 1249 g, using PRVC ventilation from birth did not alter time to extubation.

Apgar Score↗
PubMed2005

Outbreak of adenovirus type 30 in a neonatal intensive care unit.

OBJECTIVES: To describe an outbreak of adenovirus, type 30, in a neonatal intensive care unit (NICU). STUDY DESIGN: This was a retrospective, observational study. RESULTS: An outbreak of adenovirus infection occurred in an NICU. It lasted 6 months and involved 21 of 333 (6.3%) infants. The introduction of infection control measures controlled the outbreak; however, premature discontinuation of the measures resulted in a second wave of cases. The virus caused pneumonia in 7 infants, conjunctivitis in 7 infants, pneumonia and conjunctivitis in 1 infant, and upper respiratory tract illness in 1 infant. Infection was asymptomatic in 5 infants. Six infants died. Death was associated with the presence of pneumonia ( P = .0001), administration of steroids ( P = .003), and mechanical ventilation ( P = .02). Investigation into the origin of the outbreak suggested that the virus may have been introduced and spread during ophthalmologic procedures. CONCLUSIONS: Adenovirus type 30 can cause severe disease among premature infants in an NICU. Infants with severe bronchopulmonary dysplasia requiring mechanical ventilation are more likely to have development of adenovirus pneumonia and die. Standard infection control measures are effective in controlling an outbreak. Ophthalmologic procedures continue to be a potential source of adenovirus outbreaks.

Adenoviridae Infections↗
PubMed2005

Growth factors in lung development.

Organized and coordinated lung development follows transcriptional regulation of a complex set of cell-cell and cell-matrix interactions resulting in a blood-gas interface ready for physiologic gas exchange at birth. Transcription factors, growth factors, and various other signaling molecules regulate epithelial-mesenchymal interactions by paracrine and autocrine mechanisms. Transcriptional control at the earliest stages of lung development results in cell differentiation and cell commitment in the primitive lung bud, in essence setting up a framework for pattern formation and branching morphogenesis. Branching morphogenesis results in the formation of the conductive airway system, which is critical for alveolization. Lung development is influenced at all stages by spatial and temporal distribution of various signaling molecules and their receptors and also by the positive and negative control of signaling by paracrine, autocrine, and endocrine mechanisms. Lung bud formation, cell differentiation, and its interaction with the splanchnic mesoderm are regulated by HNF-3beta, Shh, Nkx2.1, HNF-3/Forkhead homolog-8 (HFH-8), Gli, and GATA transcription factors. HNF-3beta regulates Nkx2.1, a transcription factor critical to the formation of distal pulmonary structures. Nkx2.1 regulates surfactant protein genes that are important for the development of alveolar stability at birth. Shh, produced by the foregut endoderm, regulates lung morphogenesis signaling through Gli genes expressed in the mesenchyme. FGF10, produced by the mesoderm, regulates branching morphogenesis via its receptors on the lung epithelium. Alveolization and formation of the capillary network are influenced by various factors that include PDGF, vascular endothelial growth factor (VEGF), and retinoic acid. Epithelial-endothelial interactions during lung development are important in establishing a functional blood-gas interface. The effects of various growth factors on lung development have been demonstrated by gain- or loss-of-function studies in null mutant and transgenic mice models. Understanding the role of growth factors and various other signaling molecules and their cellular interactions in lung development will provide us with new insights into the pathogenesis of bronchopulmonary dysplasia and disorders of lung morphogenesis.

Gene Expression Regulation, Developmental↗
PubMed2005

Surfactant administration by transient intubation in infants 29 to 35 weeks' gestation with respiratory distress syndrome decreases the likelihood of later mechanical ventilation: a randomized controlled trial.

OBJECTIVE: To assess, among premature infants with early respiratory distress syndrome (RDS), the effect of one dose of intratracheally administered surfactant followed by extubation to nasal continuous positive airway pressure (NCPAP) on subsequent mechanical ventilation (MV), when compared with NCPAP alone. STUDY DESIGN: Randomized, blinded trial in infants 29 to 35 weeks' gestation with mild-to-moderate RDS requiring supplemental oxygen and NCPAP. Infants were randomized to intubation, surfactant treatment, and immediate extubation (surfactant group N=52), or to no intervention (control group N=53). All infants were subsequently managed with NCPAP. RESULTS: Need for later MV was 70% in the control group and 50% in the surfactant group. Surfactant group subjects had lower inspired oxygen fraction (FiO(2)) after study intervention and were less likely to require subsequent surfactant. Overall surfactant use, duration of O(2) therapy, length of stay, and bronchopulmonary dysplasia were unaffected. CONCLUSION: Among premature infants with mild-to-moderate RDS, transient intubation for surfactant administration reduces later MV.

Biological Products↗
PubMed2004

Growth factors in the fetal and neonatal lung.

Formation and orderly development of the mammalian lung results from a complex set of cell to cell and cell to matrix interactions following transcriptional regulation during pulmonary organogenesis. Transcriptional control of differentiation genes early on and epithelial-mesenchymal interactions mediated by growth factors later on, resulting in the formation of conducting airways and an extensive alveolar capillary interface, is critical for normal lung development. HNF-3beta and TTF-1 are transcription factors that are involved in gene regulation and formation and differentiation of respiratory epithelium. Studies done in early mouse embryonic lung demonstrate that a variety of peptide growth factors and their receptors are expressed early on in lung development. Signalling through the FGFR2 is critical to normal development of the distal epithelium and mesenchyme. The inductive and permissive influences of growth factors on lung development has been demonstrated by gain or loss of function experiments in early embryonic mouse lung organ culture, in transgenic and in null mutant mice. VEGF present in airway epithelial cells is involved in the maturation as well as proliferation of capillary endothelial cells. Epithelial-endothelial interactions during lung development are important in establishing a functional blood gas interface. Epithelial-mesenchymal interactions mediated by growth factors are also important in the restoration of normal alveolar architecture after lung injury. Further understanding of the role of these growth factors and their cellular interactions in bronchopulmonary dysplasia and in tissue repair following lung injury, may lead to development of better therapeutic modalities in treating these disorders.

Animals↗
PubMed2003

Comparison of breast- and formula-fed normal newborns in time to first stool and urine.

BACKGROUND: Although the time to an infant's first stool is used as a marker for a normal GI tract, there have been no studies to date which have evaluated the contribution of the first 24 hours' feeding type to time to first meconium stool, directly comparing breast feeding vs formula feeding. OBJECTIVE: To compare breast- and formula-fed healthy infants > or =34 weeks gestation in time to first stool and urine. STUDY DESIGN: A chart review of 1000 consecutive infants > or =34 weeks of gestational age admitted to the normal newborn nursery of Children's Hospital of Buffalo from June to October 2000. Infants (n=979) were grouped based on feeding type in the first 24 hours: breast-fed (n=211), formula-fed (n=540), and mixed feeding (n=228); n=21 excluded for Neonatal Intensive Care Unit admission. We initially compared the time to first stool and urine between the breast- and formula-fed groups and then examined multiple maternal and infant demographic and clinical factors for their effect on time to first stool using univariate and multivariate analyses. RESULTS: Breast-fed infants were fed earlier and more frequently than formula-fed but there was no significant difference in time to first stool (7.6 vs 7.9 hours). Breast-fed infants were earlier in time to first urine (p=0.03) (7.3 vs 8.5 hours). In multiple regression analysis, gestational age was the only significant (p=0.000) factor in predicting time to first stool. CONCLUSION: Type of feeding did not predict time to first stool but gestational age was important even in this near-term and term population of infants > or =34 weeks gestation.

Adult↗
PubMed2002

Parathyroid hormone-related protein response to hyperoxic lung injury.

Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar type II cells. Type II cell proliferation after lung injury from 85% oxygen is regulated, in part, by a fall in lung PTHrP. In this study, we investigated lung PTHrP after injury induced by >95% oxygen in rats and rabbits. In adult rats, lung PTHrP rose 10-fold over controls to 6,356 +/- 710 pg/ml (mean +/- SE) at 48 h of hyperoxia. Levels fell to 299 +/- 78 pg/ml, and staining for PTHrP mRNA was greatly reduced at 60 h (P < 0.05), the point of most severe injury and greatest pneumocyte proliferation. In adult rabbits, lung PTHrP peaked at 3,289 +/- 230 pg/ml after 64 h of hyperoxia with 24 h of normoxic recovery and then dropped to 1,629 +/- 153 pg/ml at 48 h of recovery (P < 0.05). Type II cell proliferation peaked shortly after the fall in PTHrP. In newborn rabbits, lavage PTHrP increased by 50% during the first 8 days of hyperoxia, whereas type II cell growth decreased. PTHrP declined at the LD(50), concurrent with increased type II cell division. In summary, lung PTHrP initially rises after injury with >95% hyperoxia and then falls near the peak of injury. Changes in PTHrP are temporally related to type II cell proliferation and may regulate repair of lung injury.

Age Factors↗
PubMed2002

Longitudinal, 15-year follow-up of children born at less than 29 weeks' gestation after introduction of surfactant therapy into a region: neurologic, cognitive, and educational outcomes.

OBJECTIVE: To measure the primary and secondary school-age neurologic, cognitive, and educational outcomes in a cohort of extremely premature infants born after the introduction of exogenous surfactant therapy in a circumscribed region. METHODS: Two hundred thirteen infants born at <29 weeks' gestation were cared for at a regional referral center during 1985-1987. At primary school age, neurologic and cognitive outcomes, educational achievement, school placement, health status, and socioeconomic status were determined by follow-up visit. At secondary school age, school placement and health status were evaluated by telephone interview. RESULTS: One hundred thirty-two infants survived to school age, of whom 127 (96%) were evaluated in 1992-1995 and 126 (95%) were evaluated in 2000. Mean ages were 7.0 years at first follow-up and 14.1 years at second follow-up. At primary-school age follow-up, 19 children (15%) had cerebral palsy, 24 (19%) had a general cognitive index <70, and 41 (32%) were placed in a self-contained, special classroom. Thirty-nine children (31%) had no physical or educational impairment, whereas 27 (21%) had at least 1 severe disability. At secondary school age, cerebral palsy incidence remained unchanged, whereas 36 children (29%) were placed in a special classroom. Fifty-one children (41%) had no physical or educational impairment, whereas 24 (19%) had at least 1 severe disability. Neonatal intraventricular hemorrhage and low socioeconomic status were the strongest predictors of adverse outcomes. CONCLUSIONS: Premature infants born in the surfactant era remain at high risk of neurodevelopmental compromise. Although many of these children do well, a significant minority will require intensive special educational services through secondary school age.

Adolescent↗
PubMedDate not supplied

Transforming growth factor alpha (TGF(alpha)) is increased during hyperoxia and fibrosis.

Transforming growth factor alpha (TGF(alpha)) stimulates type II alveolar epithelial cell proliferation and also is associated with fibrosis. We studied the changes in bronchoalveolar lavage (BAL) TGF(alpha) protein in a neonatal rabbit hyperoxia-fibrosis model (100% O(2) for 8 to 9 days, followed by 60% O(2) to 36 days of age). Hyperoxia increased TGF(alpha) protein and delayed the appearance of mature lower molecular weight (MW) TGF(alpha) isoforms at postnatal days 6 and 8 during the acute injury period. At 3 and 5 weeks, after chronic hyperoxia exposure, there was an increase in lower MW TGF(alpha) peptides during the fibrotic period. Keratinocyte growth factor (KGF) is also a type II cell mitogen. In vitro studies of keratinocytes suggest that KGF-induced proliferation is mediated through TGF(alpha). Intratracheal KGF instillation into adult wild-type and TGF(alpha)-null mice demonstrated that the KGF induced equivalent robust levels of proliferation in both TGF(alpha) deficient and wild-genotype mice. In conclusion, there are both quantitative and qualitative changes in TGF(alpha) protein in a hyperoxia-induced fibrosis neonatal rabbit model during periods of type II cell proliferation and fibrosis.

Administration, Inhalation↗