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Biomedical subjects

J R Hageman

Publications and source records attributed to J R Hageman.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of a prostacyclin analog in prevention of pulmonary oxygen toxicity.

Prolonged exposure to high concentrations of oxygen can result in significant lung injury, although newborn animals are tolerant relative to adults. We previously reported that relative O2 tolerance in the rabbit is lost by 10 days of age, and is coincident with a decline in lung prostacyclin. In the current study we administered iloprost, a stable prostacyclin analog, by continuous infusion to maturing rabbits exposed to greater than 95% oxygen. Compared to vehicle-treated controls, iloprost-treated rabbits had significantly lower protein in bronchoalveolar lavage fluid at 84 h, a smaller percentage of neutrophils at 65 and 84 h, and lower mortality at 96 h. The partial protection against pulmonary oxygen toxicity afforded by iloprost is likely due to its membrane stabilizing effect, and its inhibitory actions on neutrophil migration, activation, production of oxygen radicals and proteolytic enzymes.

Animals↗
PubMed1992

Evaluation of a leukotriene receptor antagonist in prevention of hyperoxic lung injury in newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury and has been associated with the development of bronchopulmonary dysplasia. Leukotrienes (LT) recruit polymorphonuclear leukocytes (PMN) to the lung, increase vascular permeability, and have therefore been postulated to play a role in the pathogenesis of hyperoxic lung injury. This study investigates ICI 198,615 (ICI), an LTD4 and LTE4 receptor antagonist in preventing hyperoxic lung injury in newborn rabbits. Matched littermates of 7-day-old rabbits received ICI (0.1 or 1.0 microM/kg/h) or vehicle alone, were exposed to greater than 95% O2, and sacrificed after 48, 72, 84 and 96 h of exposure. Bronchoalveolar alveolar lavage fluid (BAL) of the left lung was analyzed for white cell count, differential, absolute number of PMNs, total protein, and cyclooxygenase products 6-keto-PGF1 alpha, and thromboxane B2. Lung water was quantified utilizing the right lung. Results demonstrated no significant differences between the ICI groups or between the ICI groups and controls. In conclusion, the administration of the LTD4 and LTE4 receptor antagonist ICI 198,615 was insufficient to reduce the formation of pulmonary edema, reduce mortality or attenuate hyperoxic lung injury. These experiments suggest that a number of other mediators may be involved in the hyperoxic lung injury process and that the functional inhibition of a portion of the arachidonic acid cascade was not sufficient to either prevent or attenuate hyperoxic lung injury in newborn rabbits.

Animals↗
PubMed1992

Education of personnel involved in the transport program.

Inclusive in the demand for transport services is the need for an ongoing formal educational curriculum to ensure that a high standard of care is consistently provided to patients. Those who provide transport services must ensure that the staff has an adequate baseline level of training and licensure, an ongoing system of educational review, and the frequency of activity necessary to maintain skills. Team members should have an acceptable level of cognitive and technical skills to transport patients and perform needed procedures safely. Such skills may be acquired and maintained by participation in nontransport activities, through a didactic curriculum and a system of ongoing case review, through team members providing training to referring hospitals, and through a "buddy" system of supervised transport activities. While an ongoing educational curriculum and its structure remain constant, the content can and should be tailored to the type of patients transported, from the very low birth weight infant and pregnant mother to pediatric and adult patients.

Clinical Competence↗
PubMed1991

Anticardiolipin antibody-positive serum enhances endothelial cell platelet-activating factor production.

Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis.

Because previous investigations have suggested that platelet activating factor and tumor necrosis factor-alpha (TNF-alpha) are important mediators of experimental necrotizing enterocolitis in the rat, we measured platelet activating factor, acetylhydrolase (the platelet activating factor breakdown enzyme), and TNF-alpha in the plasma of 12 human neonates with necrotizing enterocolitis and eight age-matched control subjects with similar gestational ages, postnatal ages, and weights. Almost all patients with necrotizing enterocolitis had elevated plasma platelet activating factor values (18.1 +/- 3.6 ng/ml vs. 3.1 +/- 0.9 ng/ml in control subjects, p less than 0.01). Plasma acetylhydrolase activity was lower in patients than in control subjects (10.6 +/- 0.7 nmol/ml/min vs 23.0 +/- 1.4 nmol/ml/min, p less than 0.01). Plasma TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis (136 +/- 75 U/ml vs 1.5 +/- 0.8 U/ml, p less than 0.05), although the individual variation was high. There was no correlation between individual TNF-alpha and platelet activating factor levels. We conclude that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that suppressed platelet activating factor degradation contributes to the increased platelet activating factor levels; platelet activating factor and TNF-alpha may contribute to the pathophysiology of necrotizing enterocolitis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn.

Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

National survey of diagnosis and management of persistent pulmonary hypertension of the newborn.

The diagnosis and management of persistent pulmonary hypertension of the newborn remains controversial. A national survey was performed to analyze recent trends in the incidence, diagnosis, management, and survival of patients with persistent pulmonary hypertension of the neonate. Sixty-six institutions from all geographical regions responded. The overall admission incidence was 3.9% +/- 2.6%. Secondary persistent pulmonary hypertension of the neonate was more common than primary. Unexplained hypoxemia, ductal level right-to-left shunting, echocardiography, and a positive response to hyperventilation were all used frequently (in at least 79% of institutions) to diagnose persistent pulmonary hypertension of the neonate. The majority of institutions considered a positive response to hyperventilation to be determined by an increase of PaO2 by 30 mm Hg with a concomitant decrease in PaCO2 to 25 mm Hg. Approximately 70% of institutions use varying ventilator techniques (ie, with or without hyperventilation), but the majority use hyperventilation predominantly. Almost all (greater than 90%) institutions used muscle paralytic agents and pulmonary vasodilators. Tolazoline was the first choice of pulmonary vasodilator therapy. The overall survival rate of persistent pulmonary hypertension of the newborn was 77.4% +/- 13.4%. Survival rate did not differ between different geographic areas of the country. There was a trend noted for improved survival with less use of muscle paralyzing agents. Yet despite varying treatment protocols, survival rates are improving.

Carbon Dioxide↗
PubMed1989

Loss of oxygen tolerance in newborn rabbits: relationship to changes in eicosanoid and antioxidant levels.

Relative tolerance of newborn animals to hyperoxia has been reported. This study investigated the age limitation of oxygen tolerance and mechanisms for its loss. Developmental changes in lungs of normoxic New Zealand rabbits were studied on days 1, 3, 4, 5, and 10 of life. These were contrasted with newborn and 7-day-old rabbits exposed to greater than 95% O2 for 65 hours. Normoxic rabbits demonstrated a decrement in bronchoalveolar lavage (BAL) 6keto-PGF1a, thromboxane B2, and lower lung catalase, total glutathione, and superoxide dismutase with maturation. Newborns were more tolerant to oxygen than 7-day-old rabbits. Oxygen exposure beginning on day 1 did not result in identifiable lung damage. Exposure beginning on day 7 resulted in microscopic evidence of injury and significant increases in BAL white cells, neutrophils and protein, and a trend toward higher BAL LTB4 compared to normoxic age-matched controls. Antioxidants were higher in the hyperoxic 7 day-olds, but remained lower than values in hyperoxic newborns. These results suggest that loss of oxygen tolerance in maturing rabbits is related to a developmental decrement in antioxidants and prostacyclin.

Animals↗
PubMed1989

Role of eicosanoids in relative oxygen tolerance of newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury, although newborn animals are more oxygen-tolerant than adults. Mechanisms affording tolerance to the newborn are incompletely understood. This study examined the hypothesis that eicosanoids play a significant role in newborn oxygen tolerance. One litter of term newborn albino rabbits and 15 adult rabbits were exposed to 65 hours of greater than 95% O2. An additional litter of newborns served as a normoxic control. Normoxic newborn rabbits had very high quantities of 6-keto-PGF1a and low TXB2 in bronchoalveolar lavage (BAL) fluid. Sixty-five hours of oxygen exposure in newborn rabbits produced no evidence of lung injury on light microscopy, 97% of BAL white cells were alveolar macrophages and BAL protein was low. An equal period of oxygen exposure produced significant lung injury in adult rabbits. BAL fluid from oxygen-injured adults contained a 17-fold greater percentage of PMN and 16-fold higher protein than oxygen-exposed newborns. Hyperoxic adults had significantly lower 6-keto-PGF1a, and significantly higher LTB4 and LTC4 in BAL compared to hyperoxic newborns. This study confirms the hypothesis of relative oxygen tolerance in newborn rabbits compared to adults, and suggests that this tolerance may have been afforded by higher pulmonary levels of the protective prostacyclin metabolite.

Animals↗
PubMed1989

Oleic acid lung injury increases plasma prostaglandin levels.

To determine whether lung injury causes increased plasma prostaglandin (PG) levels, 35 rabbits received oleic acid and 35 served as controls. Half of each group also received 4 ml/kg of Intralipid over one hour and at least five in each subgroup received indomethacin 7.5 mg/kg. Arterial and venous plasma concentrations of PGE2, 6-keto-PGF1 alpha, and PGF2 alpha-M were measured. Venous PGE2 was significantly higher in the oleic acid-injured than in the normal lung group, 1560 +/- 270 (Mean +/- SEM) versus 880 +/- 140 pg/ml (p less than .05). Plasma levels were reduced by 50% with indomethacin, but PGE2 levels remained significantly higher than in the normal lung group, 850 +/- 180 versus 480 +/- 60 for arterial (p less than .05) and 820 +/- 140 versus 480 +/- 80 for venous (p less than .05), respectively. PGF2 alpha-M levels were significantly higher in the lung injury group, 240 +/- 50 versus 50 +/- 40 pg/ml for arterial (p less than .05) and 220 +/- 50 versus 95 +/- 40 for venous (p less than .05), respectively. These lung injury-related increases in PGE2 and PGF2 alpha-M appear related both to increased pulmonary production and to decreased pulmonary clearance. With Intralipid infusion, however, arterial PGE2 increased by 500 +/- 260 pg/ml compared to baseline (p less than .05) with no change in venous PGE2, indicating in this instance that the increase in arterial PGE2 levels is related to increased pulmonary production.

Animals↗
PubMed1989

Prostaglandin E1 infusion fails to prevent hyperoxic lung injury in adult rabbits.

Arachidonic acid (AA) metabolites may be important mediators in the hyperoxic lung injury process. We have previously demonstrated, in an adult model of hyperoxic lung injury, that bronchoalveolar lavage (BAL) fluid levels of AA metabolites of the cyclooxygenase pathway increase before evidence of overt injury. Nonselective inhibition with indomethacin or dexamethasone failed to ameliorate the injury process, possibly because production of prostaglandin I2 (PGI2) was suppressed. In this study, we attempted to ameliorate hyperoxic lung injury using an infusion of prostaglandin E1 (PGE1), since PGE1 has some of the potentially protective effects of PGI2. Thirty-two adult rabbits were exposed to greater than 95% oxygen; eight served as controls and 24 received PGE1 infusion (five, nine, and ten received 0.1, 0.06, and 0.03 micrograms/kg.min, respectively). At the end of the 65-h exposure period, BAL of the left lung was performed; the right was saved for light microscopy. PGE1 infusion at the 0.06 and 0.03-micrograms/kg.min doses resulted in significantly fewer polymorphonuclear leukocytes (PMN) in BAL fluid (p less than .05). However, PGE1 infusion did not significantly ameliorate the lung injury process. In summary, although PGE1 infusion inhibited the influx of PMN into the lung, treatment did not result in any significant amelioration of the hyperoxic lung injury process.

Alprostadil↗
PubMed1989

Perinatal management of meconium staining of the amniotic fluid.

The pathogenesis of meconium passage and the pathophysiology of meconium aspiration are reviewed. Intrapartum and neonatal strategies for the prevention of meconium aspiration syndrome are presented in historical perspective, and newer interventions are appraised.

Amniotic Fluid↗
PubMed1988

Outcome of persistent pulmonary hypertension in relation to severity of presentation.

Since the initial description of persistent pulmonary hypertension of the newborn (PPHN), the management of these infants has been controversial. A variety of therapeutic modalities, such as extracorporeal membrane oxygenation, have been utilized. Early recognition of a group of patients with PPHN who might require aggressive therapy would be clinically useful. Highest alveolar-arterial oxygen gradient at or near diagnosis was evaluated retrospectively in 53 patients with PPHN in relation to survival, aggressiveness of management, and frequency of pulmonary complications (air leak and broncho-pulmonary dysplasia). Highest alveolar-arterial oxygen gradient was a good early predictor of nonsurvival and was significantly higher in nonsurvivors compared with survivors (mean [+/- SD], 618 +/- 23 mm Hg vs 521 +/- 128 mm Hg). Values of 600 mm Hg or greater were more frequent in the nonsurvivors compared with the survivors (92% vs 37%). Air leak also proved to be a good predictor of nonsurvival.

Humans↗
PubMed1988

Respiratory pattern at hospital discharge in asymptomatic preterm infants.

Pneumogram (PG) recordings were performed in 87 very low birthweight (VLBW) asymptomatic infants just prior to hospital discharge to determine the relationships between: 1) a prior history of apnea of prematurity (AOP) and cardiorespiratory pattern; and 2) cardiorespiratory pattern at hospital discharge and postconceptional age. Apnea density (A6/D%) and longest apnea were significantly greater in those with (n = 66), versus without (n = 21) a prior history of AOP (P less than 0.05 and P less than 0.01, respectively). Although PG values for the 21 VLBW infants without a prior history of AOP did not differ significantly from those of full-term infants, for the 66 VLBW infants with a prior AOP history A6/D% (P less than 0.01), episodes of periodic breathing (P less than 0.05) and longest apnea (P less than 0.001) were significantly greater compared with full-term infants. Postconceptional age was significantly less in the VLBW infants with A6/D% values above, compared with those within the 95th percentile for normal infants (median age, 36 and 37.5 weeks; P = 0.01). Therefore, respiratory pattern abnormalities in asymptomatic VLBW infants ready for hospital discharge are related to a prior history of AOP and may be significantly higher than in full-term infants at the postconceptional ages at which hospital discharge now tends to occur.

Apnea↗
PubMed1988

Monitoring of critically ill infants and children.

The strategies for monitoring infants and children in the intensive care setting differ from the strategies used to monitor adults. This article highlights the physiologic differences between infants and children and adults that affect these methods. The technical aspects of monitoring infants and children are also discussed.

Adolescent↗