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At least 307 records · Page 17Linked to original sources
PubMed1999

Measurement of protein flux with positron emission tomography in neonates.

AIM: To determine whether abnormal transvascular protein flux can be measured with positron emission tomography (PET) in neonates with respiratory distress syndrome (RDS). METHODS: Fourteen infants with normal gas exchange (non-RDS group) underwent one PET measurement and 12 infants with RDS (the RDS group) underwent two measurements of protein flux, as determined by the pulmonary transcapillary escape rate for 68Gallium labelled transferrin (PTCER). RESULTS: The mean PTCER for the RDS infants (132 +/- 39 10(-4)/min) was significantly greater than that for infants without RDS (75 +/- 27 10(-4)/min). PTCER did not change between measurements in the infants with RDS, including five who received and responded to surfactant replacement between the two scans. CONCLUSIONS: Increased transvascular flux of large molecular weight proteins complicates RDS in preterm infants. PET provides a tool with which to evaluate the processes that contribute to pulmonary dysfunction in neonates.

Capillary Permeability↗
PubMed2005

[Rat alveolar type II injured by bleomycin].

OBJECTIVE: To explore dysfunction mechanism of rat alveolar type II (AT-II) injured by bleomycin (BLM). METHODS: SD rats were injected with a single intratracheal dose of bleomycin or control saline. On day 7, 14, and 28 following intratracheal bleomycin or saline instillation, animals were killed under overdose of 1.5% sodium pentobarbital (0.25 ml/100 g, i.p.) and bronchoalveolar lavage fluid (BALF) from the lung was tested for the activity of pulmonary surfactant (PS) by the Whihelmy Film Balance. Several concentrations of bleomycin stimulated the culture of rat AT-II cells, and surfactant protein (SP) A, B, and aquaporin-1 (AQP) mRNA were analyzed by fluorescent quantitative polymerase chain reaction (FQ-PCR). RESULTS: The activity of PS and hypoxemia significantly decreased on day 7 and improved on day 14 and completely recovered to normal status on day 28. SP-A, B, and AQP-1 mRNA expression in BLM-stimulated group were significantly lower than those in the control group (P<0.001). CONCLUSION: BLM-injured AT-II cells decrease the levels of SP-A, B, and AQP-1 mRNA and cause PS dysfunction, resulting in hypoxemia and pneumonedema.

Animals↗
PubMed2003

Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction.

OBJECTIVE: To review the effects of chronic alcohol abuse on the incidence, severity, and pathogenesis of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. DATA SOURCES: A summary of published medical literature from MEDLINE search files and other reviews published concerning chronic alcohol abuse and critical illness. DATA SUMMARY: A history of chronic alcohol abuse is associated with an increased incidence and severity of ARDS in critically ill patients. In two separate epidemiologic studies, involving 571 intensive care patients, chronic alcohol abuse was a significant comorbid variable that increased the incidence of ARDS by nearly three-fold and was associated with more severe nonpulmonary organ dysfunction. In addition, nearly 50% of all ARDS patients had a significant history of chronic alcohol abuse, making the association between chronic alcohol abuse and ARDS a common scenario in the intensive care unit. By using animal models of chronic ethanol ingestion, researchers have identified alcohol-mediated alterations in epithelial and endothelial cell function, surfactant synthesis and secretion, alveolar-capillary barrier function, and lung matrix content and composition. More importantly, similar changes have been reported in humans with a history of chronic alcohol abuse. Individuals with a history of chronic alcohol abuse have decreased concentrations of glutathione in the epithelial lining fluid of the lung, which do not significantly increase after 1 wk of abstinence from alcohol. The total protein concentration in the epithelial lining fluid also is increased in these individuals with a history of chronic alcohol abuse compared with healthy controls, suggesting alterations in alveolar-capillary barrier function. CONCLUSIONS: Chronic alcohol abuse is associated with an increased incidence of ARDS and the severity of multiple organ dysfunction. This research has implications in understanding the diagnosis of, and prognosis for, critically ill patients who are at risk of developing ARDS. It also may lead to the development of novel therapies for those patients at greatest risk of acute lung injury as a consequence of chronic alcohol abuse.

APACHE↗
PubMed1983

Left ventricular performance and regional blood flows before and after ductus arteriosus occlusion in premature lambs treated with surfactant.

The hemodynamic consequences of patent ductus arteriosus (PDA) were studied during the first few hours of life (1.9 +/- 0.7 hours) in 13 mechanically ventilated, surfactant-treated, preterm lambs (gestational age of 120-124 days). Cardiovascular pressures, left ventricular (LV) performance and regional blood flows were measured using cine left ventriculography and radionuclide-labeled microspheres before and after occlusion of the PDA with a catheter balloon. Before occlusion, the left-to-right shunt was 44 +/- 13%; after occlusion the shunt was negligible (2%). Heart rate (164 +/- 17 beats/min), LV end-diastolic pressure (5 +/- 3 mm Hg), ejection fraction (74 +/- 8%) and cardiac output (241 +/- 13 ml . min-1 . kg-1) were normal and did not change after ductus occlusion. However, "effective" systemic blood flow increased significantly after occlusion (130 +/- 53 vs 228 +/- 93 ml . min-1 . kg-1, p less than 0.001), as did blood flow to organs such as the brain, myocardium and gastrointestinal tract. The reduction of systemic blood flow in the presence of a left-to-right PDA shunt may be responsible for many early pathologic manifestations of the PDA "syndrome" of prematurity even in the absence of overt LV dysfunction.

Animals↗
PubMed1991

Taiwan National Poison Center survey of glyphosate--surfactant herbicide ingestions.

Between January, 1986 and September, 1988, the Taiwan National Poison Center recorded 97 telephone consultations (49 male, 48 female) on cases of ingestion of glyphosate-surfactant herbicide concentrate containing the isopropylamine salt of glyphosate (N-phosphonomethyl glycine, CAS 1071-83-6) and a non-ionic tallow amine surfactant. Eleven of the cases resulted in fatalities, all among those attempting suicide. The average amount ingested by survivors was 120 +/- 112 mL and by nonsurvivors was 263 +/- 100 mL (p less than or equal to 0.0001). The average age of survivors was 35 +/- 15 years compared to 54 +/- 11 years for fatalities (p less than or equal to 0.0002). Irritation of the oral mucous membrane and gastrointestinal tract was the most frequently reported effect. Other effects recorded were pulmonary dysfunction, oliguria, metabolic acidosis, hypotension, leukocytosis and fever. Fourteen patients received either atropine or pralidoxime plus atropine despite the fact that glyphosate does not inhibit acetylcholinesterase. Thirteen percent of patients received a urine test for paraquat or treatment customarily used for paraquat ingestion, possibly reflecting similar initial presentations following ingestion of these two herbicides. Laboratory differentiation is essential if any doubt exists about which herbicide was ingested. Patients ingesting large volumes of concentrated glyphosate-surfactant herbicide formulations require close observation and supportive treatment.

Accidents↗
PubMed2006

[The application of individualized ventilation strategies in acute respiratory distress syndrome].

OBJECTIVE: To explore better ventilation strategies above lower-tidal-volume (LTV) strategy to protect lung function and improve outcome in acute respiratory distress syndrome (ARDS). METHODS: Thirty ARDS patients were enrolled in Department of Critical Care Medicine of Peking Union Medical College Hospital from July, 2004 to June, 2005. They were randomly allocated into two groups, LTV group and individual ventilation (IV) group. Patients received 6 ml/kg tidal volume (V(T)) and high positive end-expiratory pressure (PEEP) in LTV group. In IV group, static pressure-volume (P-V) curve was measured daily, and PEEP and V(T) were set based on P-V variation, and the open-lung potential was evaluated before recruitment maneuvers. The clinical effect, the degree of lung injury and other outcome indicators in two groups were assessed. RESULTS: The mortality rate in 28 days of IV group (35.7%) was lower than that of LVT group (57.2%, chi(2) = 1.265, P > 0.05). The serum surfactant-associated protein D (SP-D) expression in the third and the seventh day of IV group [154 (91 - 217), 149 (91 - 206) mg/L] were higher than those before enrollment [140 (80 - 200) mg/L]; and the IL-8 expression in the third and the seventh day of IV group [179 (122 - 236), 210 (100 - 321) ng/L] were higher than those before enrollment [210 (132 - 289) ng/L]; but all showed no significant difference [chi(2) = 1.265, Z = 1.079, 1.741, -0.879, 0.471, respectively, all P > 0.05]. The free-ICU days in 28 days and free-organ-dysfunction days of IV group [11 (5 - 16) d, 13 (6 - 18) d] were significantly higher than that of LTV group [3 (0 - 8) d, 3 (0 - 7) d, Z = -2.277, -2.372 respectively, all P < 0.05]. The PEEP, V(T), partial pressure of carbon dioxide in arterial blood (PaCO2), the plateau pressure (Pplat) of initial 3 days after enrollment in IV group [(11 +/- 2) cm H2O (1 cm H2O = 0.098 kPa), (511 +/- 66) ml, (37 +/- 5) mm Hg (1 mm Hg = 0.133 kPa), (21 +/- 5) cm H2O] were significant different with those of LTV group [(16 +/- 3) cm H2O, (407 +/- 58) ml, (47 +/- 8) mm Hg, (26 +/- 4) cm H2O, t = -8.019, 6.501, -4.311, -4.823, all P < 0.01]. CONCLUSIONS: Compared with LTV and high PEEP therapy, IV strategies are feasible for decreasing PEEP and Pplat, increasing tidal compliance and V(T), and avoiding CO2 retention. It also increased free-ICU days and free-organ-dysfunction days.

Adult↗
PubMed2000

Intravenous detergent poisoning.

CASE REPORT: In the literature regarding surfactant poisoning, the route of exposure has almost always been oral. We report a case in which about 40 mL of bath detergent for home use was self-injected. The primary pathophysiologic effects were relative hypovolemia and cardiac dysfunction. The patient experienced frequent ventricular tachycardia, acute renal failure, rhabdomyolysis, hemolysis, and coagulation dysfunction. Intensive care included the administration of antiarrythmial agents and hemodialysis. The patient survived and was discharged from our hospital without sequelae.

Acute Kidney Injury↗
PubMed2002

Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease.

Types A and B Niemann-Pick disease (NPD) are lipid storage disorders caused by the deficient activity of acid sphingomyelinase (ASM). In humans, NPD is associated with the dysfunction of numerous organs including the lung. Gene targeting of the ASM gene in transgenic mice produced an animal model with features typical of NPD, including pulmonary inflammation. To assess mechanisms by which ASM perturbed lung function, we studied lung morphology, surfactant content, and metabolism in ASM-deficient mice in vivo. Pulmonary inflammation, with increased cellular infiltrates and the accumulation of alveolar material, was associated with alterations in surfactant content. Saturated phosphatidylcholine (SatPC) content was increased twofold, and sphingomyelin content was increased 5.5-fold in lungs of the ASM knockout (ASMKO) mice. Additional sphingomyelin enhanced the sensitivity of surfactant inhibition by plasma proteins. Clearance of SatPC from the lungs of ASMKO mice was decreased. Catabolism of SatPC by alveolar macrophages from the ASMKO mouse was significantly decreased, likely accounting for decreased pulmonary SatPC in vivo. In summary, ASM is required for normal surfactant catabolism by alveolar macrophages in vivo. Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactant function observed in the ASM-deficient mouse.

Animals↗
PubMed2003

Prostaglandin E2 induces upregulation of Na+ transport across Xenopus lung epithelium.

The apical mucus on pulmonary epithelia is not only critical for physiological functions such as gas exchange or inflammatory processes, but also contains surfactants and multiple molecules that mediate cellular responses. A tight control of transepithelial ion transport maintains viscosity of this layer and, e.g., the amiloride-sensitive sodium channels (ENaCs) in lung epithelia of vertebrates are the most important regulatory sites for transcellular sodium uptake. Dysfunction of this sodium transport results in reduced liquid absorption and causes massive problems with gas exchange. We used dissected lungs of Xenopus laevis in Ussing chambers to investigate the influence of prostaglandin E2 (PGE2) on the regulation of short-circuit current (ISC) and amiloride-sensitive sodium absorption (Iami). Apical application of PGE2 (1 microM) increased ISC by 38% and Iami by approximately 60%. In contrast, a different prostaglandin, PGI2, neither affected ISC nor Iami. Forskolin increased current to a similar magnitude and preincubation of the lung with an RP-isomer of cyclic AMP, an inhibitor of protein kinase A (PKA), abolished the effects of both PGE2 and forskolin. Transepithelial Na+ uptake was also upregulated by the prostaglandin receptor agonists misoprostol and sulprostone. The Iami in Xenopus oocytes that heterologously expressed ENaCs was not affected by PGE2.

Animals↗
PubMed2004

Epidemiology of preterm birth and neonatal outcome.

In industrialized countries, 5-11% of infants are born preterm (<37 weeks' gestation), and the rate has been increasing since the early 1980s. Preterm births account for 70% of neonatal deaths and up to 75% of neonatal morbidity, and contribute to long-term neurocognitive deficits, pulmonary dysfunction and ophthalmologic disorders. In the past several decades, major progress has been made in improving the survival of extremely premature newborns, mostly attributable to timely access to effective interventions that ameliorate prematurity-associated mortality and morbidity such as antenatal administration of corticosteroids and exogenous surfactant therapy, rather than preventing preterm births. However, the societal and healthcare costs to care for survivors with severe morbidity and neurological handicaps remain substantial. Future research should concentrate on the ways to reduce long-term health sequelae and developmental handicaps among survivors of infants born preterm, as well as elucidating the mechanisms and aetiology of preterm births.

Female↗
PubMed1994

Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses.

We tested the hypothesis that pulmonary surfactant-associated lectins--surfactant proteins A and D (SP-A, and -D)--contribute to initial protective mechanisms against influenza A viruses (IAVs). SP-D potently inhibited hemagglutination activity of several strains of IAV as well as causing viral aggregation. SP-D enhanced neutrophil binding of IAV and neutrophil respiratory burst responses to the virus. Neutrophil dysfunction resulting from IAV exposure was diminished when the virus was pre-incubated with SP-D. Each of these effects was mediated by the calcium-dependent carbohydrate-binding property of SP-D. Native SP-D preparations of both human and rat origin, as well as recombinant rat SP-D, had similar activity. SP-A also inhibited IAV hemagglutination activity. We have previously reported that related mammalian serum lectins (mannose-binding lectin [MBL] and conglutinin) have similar effects. SP-D was at least 10-fold more potent at causing hemagglutination inhibition than were SP-A or MBL. SP-D was shown to contribute to potent anti-IAV activity of human bronchoalveolar lavage fluid. These results suggest that SP-D--alone, and in conjunction with SP-A and phagocytic cells--constitutes an important component of the natural immune response to IAV infection within the respiratory tract.

Animals↗
PubMed1997

Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice.

Genetic ablation of the murine SP-B gene in transgenic mice caused lethal perinatal respiratory distress in homozygous offspring, whereas heterozygous SP-B (+/-) mice survived postnatally. In adult SP-B(+/-) mice, surfactant protein B mRNA and the alveolar lavage SP-B protein were reduced by 50% compared with wild-type littermates, consistent with the inactivation of a single SP-B allele. Expression of SP-A, SP-C, and SP-D proteins was not affected in SP-B(+/-) mice. Heterozygous SP-B(+/-) mice reached maturity in numbers expected by Mendelian inheritance of a recessive gene. Lung morphology and both intracellular and extracellular phospholipid pool size and composition were unaltered in the SP-B(+/-) mice. Despite normal survival, pulmonary function studies demonstrated a consistent decrease in lung compliance in SP-B(+/-) mice. Abnormalities of inflation/deflation curves demonstrated airway collapse at low deflation pressures. Residual volumes were increased in the SP-B(+/-) mice. In summary, SP-B mRNA and SP-B protein were reduced by 50% in SP-B(+/-) mice, resulting in abnormalities of lung compliance and air trapping, suggesting a potential susceptibility to pulmonary dysfunction associated with SP-B deficiency.

Animals↗
PubMed2005

Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma.

The mechanisms of cell death and the progressive degeneration of neural tissue following traumatic brain injury (TBI) have come under intense investigation. However, the complex interactions among the evolving pathologies in multiple cell types obscure the causal relationships between the initial effects of the mechanical trauma at the cellular level and the long-term dysfunction and neuronal death. We used an in vitro model of neuronal injury to study the mechanisms of cell death in response to a well-defined mechanical insult and found that the majority of dead cells were apoptotic. We have previously reported that promotion of membrane repair acutely with the non-ionic surfactant poloxamer 188 (P188) restored cell viability to control values at 24 h postinjury. Here, we showed that P188 significantly inhibits apoptosis and prevents necrosis. We also examined the role of mitogen-activated protein kinases (MAPKs) in cell death. There was a rapid, transient activation of extracellular signal-regulated kinases, c-Jun N-terminal kinase, and p38s after mechanical insult. Of these, activation of the proapoptotic p38 was the greatest. Treatment with P188 inhibited p38 activation; however, direct inhibition of p38 by SB203580, which selectively inhibits the activity of the p38 MAPK, provided only partial inhibition of apoptosis and had no effect on necrosis. These data suggest that multiple signaling pathways may be involved in the long-term response of neurons to mechanical injury. Furthermore, that the membrane resealing action of P188 provides such significant protection from both necrosis and apoptosis suggests that acute membrane damage due to trauma is a critical precipitating event that is upstream of the many signaling cascades contributing to the subsequent pathology.

Animals↗
PubMed2004

Acute lung injury as an adverse event of gefitinib.

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is an effective treatment for patients with non-small cell lung cancer (NSCLC). Some investigators have recently reported several patients complicated by acute lung injury after the initiation of gefitinib administration. In this report, we investigated the efficacy and adverse events during treatment with gefitinib. The subjects of this study were all of the 110 patients with NSCLC who were treated in our hospital and its eight branch hospitals. Patients received gefitinib at a dose of 250 mg once daily. The response rate was 30%. The frequently reported adverse events were skin disorders, gastrointestinal disturbances, liver dysfunction and acute lung injury. Five of the 12 patients who were considered to have suffered acute lung injury died of progressive respiratory failure. Of the nine patients who had pulmonary fibrosis before use of gefitinib, five developed acute lung injury during the treatment. Sera from three of the 12 patients were evaluated and all three showed increases of surfactant protein (SP)-A, SP-D and KL-6. We conclude that gefitinib was clinically useful. However, several patients suffered acute lung injury which could have been caused by gefitinib. A detection system including SP-A, SP-D and KL-6 as prime candidates as markers should be established as promptly as possible. Clinicians should be aware that treatment of NSCLC with gefitinib involves the risk of acute lung injury and therefore careful consideration should be given before deciding whether or not gefitinib is indicated for treatment. Further study is necessary to elucidate the mechanism of acute lung injury by gefitinib.

Adult↗
PubMed2000

Ventilator-induced lung injury and implications for clinical management.

OBJECTIVE: To review recent studies in pathogenesis and management of ventilator-induced lung injury. DATA SOURCES: Articles and published reviews on ventilator-induced lung injury, barotrauma and acute lung injury. SUMMARY OF REVIEW: This review summarises the important differences between clinically apparent 'barotrauma' and the more subtle changes in lung structure and function associated with ventilation. Of great importance is the understanding that as the underlying lung injury worsens, the degree of injury from mechanical ventilation increases. An inflammatory process results from mechanical stimuli and this may contribute to distant organ dysfunction. A great deal of knowledge has been obtained from the use of animal models, however, one must be cautious about extrapolating these findings directly to the clinical setting without the use of adequately designed clinical trials. Tidal volume reduction and higher levels of PEEP and recruitment manoeuvres should be employed given the available evidence. The use of high frequency techniques, surfactant therapy despite their past track record, may prove to be exciting 're-discoveries'. CONCLUSIONS: Ventilator-induced lung injury is an iatrogenic disturbance that increases morbidity and mortality associated with acute respiratory distress syndrome. Tidal volume reduction and increased levels of PEEP have reduced inflammatory mediators and the mortality associated with ARDS.

Journal Article↗
PubMed1999

Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury.

Surfactant protein-B (SP-B) is a small, hydrophobic peptide that plays a critical role in pulmonary function and surfactant homeostasis. To determine whether SP-B protects mice from oxygen-induced injury, heterozygous SP-B(+/-) gene-targeted mice and wild-type SP-B(+/+) littermates were exposed to hyperoxia (95% oxygen for 3 d) or room air. Although specific lung compliance in room air in SP-B(+/-) mice was slightly reduced as compared with that in SP-B(+/+) mice, it was reduced more markedly during hyperoxia (46% versus 25% decrease, respectively). The larger decrease in lung compliance in SP-B(+/-) mice was associated with increased severity of pulmonary edema, hemorrhage and inflammation, lung permeability and protein leakage into the alveolar space. Hyperoxia increased SP-B messenger RNA (mRNA) and total protein concentrations by 2-fold in SP-B(+/+) and SP-B(+/-) mice, but decreased the abundance of SP-B protein in lavage fluid relative to total protein only in SP-B(+/-) mice. Hyperoxia increased SP-B expression, but apparently not enough to maintain SP-B function and lung compliance in the presence of increased protein leakage in SP-B(+/-) mice. Increased alveolar-capillary leakage and relative deficiency of SP-B may therefore contribute to oxygen-induced pulmonary dysfunction in SP-B(+/-) mice. These data support the concept that SP-B plays an important protective role in the lung.

Animals↗
PubMed2007

The alcoholic lung: epidemiology, pathophysiology, and potential therapies.

Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.

Alcoholism↗