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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse alveolar damage (DAD) is usually considered a generalized lung process. During five years the authors observed 83 patients with generalized DAD in 827 adult autopsies (10.1%) and 10 patients with identical, but localized, lesions. The authors propose the term regional alveolar damage (RAD) to designate localized "DAD." RAD was unilateral in six patients and most frequently involved the upper lobe. All ten patients had chronic systemic diseases and presented with life-threatening illnesses. The probable causes of RAD were multifactorial and included hypotensive shock, septicemia, pneumonia, hyperoxia, and pancreatitis. All patients developed respiratory failure, requiring supplemental oxygen and, in nine patients, mechanical ventilation. Chest roentgenograms revealed alveolar or combined alveolar and interstitial infiltrates that corresponded to the lesions found at autopsy. The reasons for localization of RAD within the lung are unclear, but the presence of proliferative lesions and frequent involvement of the upper lobe suggests that RAD is not simply an early phase of DAD and implicates additional pathogenetic factors.
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PMID:Regional alveolar damage (RAD). A localized counterpart of diffuse alveolar damage. 266 70

Although adequate tissue oxygenation is essential to maintain cellular metabolism, the use of hyperoxia to improve oxygen delivery or to improve metabolic performance is controversial. For example, supplemental inspired oxygen is reportedly beneficial in the treatment of some experimental infections; however, oxygen therapy also has well-documented adverse side effects. To evaluate the effect of increased inspired oxygen concentration (FIO2) in animals with fulminant sepsis, 117 Sprague-Dawley rats underwent cecal ligation and puncture. Animals were then exposed to an FIO2 of either 0.21, 0.4, or 0.8. Twenty sham-operated controls had no mortality with any FIO2. Increasing the FIO2 increased mortality from 70% to 85% in animals receiving 40% O2, and to 100% in those receiving 80% O2. Autopsies revealed mild pulmonary oxygen toxicity with 80% O2 exposure in both control and septic animals, but normal lung histologic appearance in animals receiving lower levels of oxygen. Arterial blood gases documented maintenance of oxygenation and ventilation. Thus, pulmonary oxygen toxicity does not appear to be the mechanism for increased mortality. Supplemental oxygen may worsen, rather than improve, survival after fulminant infection.
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PMID:The effects of hyperoxia during fulminant sepsis. 198 32

A major nonrespiratory function of the mammalian lung is that of a polymorphonuclear leukocyte reservoir. Within this reservoir, granulocytes are distributed between marginating and circulating pools. Under normal conditions these cells release little, if any, toxic metabolites. Situations which facilitate chemotactic release, activation of complement, or prolonged lowering of pulmonary blood flow lead to sequestration of large numbers of polymorphonuclear leukocytes in the lungs. If these polymorphonuclear leukocytes are then stimulated to release toxic oxygen species, proteases or other metabolites, existing defense mechanisms are overwhelmed and lung injury results. Anaphylatoxins generated by complement activation, humoral factors released from platelets or macrophages, and activation of the kallikrein-kinin and coagulation systems, may exacerbate damage to the alveolar-capillary membrane. Permeability of this membrane increases, there is interstitial and then alveolar edema, with subsequent pulmonary dysfunction. While there is little doubt that this scenario holds true for some experimental models of acute lung injury, its applicability to adult respiratory distress syndrome is still controversial. Nevertheless, adult respiratory distress syndrome does arise under conditions facilitating chemotactic factor release from macrophages (e.g. hyperoxia), in situations where widespread activation of complement occurs (e.g. sepsis, trauma, microemboli), and in shock conditions where pulmonary blood flow is often lowered. Correlations exist between adult respiratory distress syndrome and activation of complement, acute neutropenia, sequestration of polymorphonuclear leukocytes and enhanced functional and metabolic activity of granulocytes. Although these findings suggest that polymorphonuclear leukocytes are an important factor in the pathogenesis of adult respiratory distress syndrome, its precise role remains to be determined.
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PMID:The role of the polymorphonuclear leukocyte in the pathogenesis of the adult respiratory distress syndrome. 383 38

Hyperoxia impairs cytoskeleton-dependent phagocytic functions in polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs). To investigate the effect of different oxygen concentrations on the cytoskeleton, in particular the microtubule (MT) and microfilament (MF) system, the fluorescence pattern of Concanavalin A (Con A) receptors in AMs and PMNs was observed. Cells were obtained from guinea-pigs exposed to different oxygen concentrations. The exposure of guinea-pigs to oxygen concentrations of up to 50% induced in AMs and PMNs mainly spontaneous Con A capping, demonstrating an altered MT system. Oxygen tensions above 50% lead to an increased number of AMs and PMNs exhibiting a patchy Con A fluorescence distribution. Even in the presence of the microtubule-disrupting agent colchicine most AMs and PMNs were unable to form a Con A cap fluorescence distribution under these high oxygen tensions. This study demonstrates that the exposure of guinea-pigs to an oxygen concentration greater than 50% increases the relative number of AMs and PMNs demonstrating a patchy distribution of Con A. This patchy fluorescence pattern is associated with a severe cytoskeletal defect, i.e. MT and MF disruption. The various leukocyte function defects induced by hyperoxia, demonstrated in previous studies, are based on this MT and MF alteration in AMs and PMNs, representing an additional sepsis-promoting factor during hyperoxia.
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PMID:Concanavalin A distribution in polymorphonuclear leukocytes and alveolar macrophages during hyperoxia. 613 6

Yellow staining of central nervous system (CNS) nuclei occurs in the brains of some neonates, despite low levels of serum bilirubin. Two conditions appear to be important in the evolution of this form of kernicterus: prematurity and asphyxia. In a seven year retrospective study of a large neonatal autopsy population, 102 cases had kernicterus as indicated by selective macroscopic yellow staining and microscopic damage within specific CNS nuclei. Neuropathological study disclosed minor variations and numerous similarities in the manifestations of kernicterus in the asphyctic premature neonate with low levels of serum bilirubin, as compared to kernicterus in the full-term neonate with high levels of serum bilirubin. Acidosis, hypoxia, hyperoxia, hypothermia and sepsis have been considered significant risk factors, but recent comparative clinical studies have not defined predictive indices. Analysis of this disorder is difficult because of the concurrence of other complications of asphyxia and its pathological correlates in premature infants. Diagnostic difficulties are also compounded by variations in the definitions of kernicterus as used by different investigators.
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PMID:The neuropathology of kernicterus in the premature neonate: diagnostic problems. 669 27

The development of bacterial infections is a common complication during treatment with high concentrations of oxygen. To study the effect of hyperoxia on phagocytes, the adherence, chemotaxis, ingestion rates, degranulation as well as the bactericidal activity were measured in alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs) obtained from guinea pigs exposed to 85% oxygen. The animal exposure to a Fi O2 of 85% impaired the adherence to nylon-wool, the chemotactic activity and the phagocytic rate of paraffinoil-droplets of AMs and PMNs. In AMs the secretion of beta-glucuronidase upon stimulation with opsonized zymosan was also diminished. In addition, the bacterial activity of AMs and PMNs demonstrated a reduction of 50%. These phagocytic defects may be caused by cytoskeleton alteration, induced by the increase of oxygen derived metabolites, representing an additional sepsis promoting factor during hyperoxia.
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PMID:Effects of hyperoxia on phagocytosis. 711 85

Hyperoxic ventilation, used to prevent hypoxemia during potential periods of hypoventilation, has been reported to paradoxically decrease whole body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve whole body VO2 and prevent deterioration of oxygenation in gastric mucosal tissue during hyperoxia. Thirty-eight patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to sepsis syndrome, were included in this randomized experiment. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, FIO2 < 0.5). A gastric tonometer was placed to measure the gastric intramucosal pH (pHi), which indirectly assesses nutritive blood flow to the mucosa. Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg.kg-1 NAC (n = 19) or placebo (n = 19) in 250 ml 5% dextrose intravenously over a period of 15 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (FIO2 = 1.0), and 60 min after resetting the original FIO2. There were no significant differences between groups in any of the measurements before treatment and after the return to baseline FIO2 at the end of the study. NAC, but not placebo infusion, caused a slight but significant increase in cardiac output and decrease in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-acetylcysteine preserves oxygen consumption and gastric mucosal pH during hyperoxic ventilation. 788 69

A 9-year retrospective review of 1,242 admissions to a tertiary burn center identified 137 patients who were intubated and ventilated for a critical airway or pulmonary problem. These patients varied in age from 2 months to 18 years with an average total body surface area (TBSA) burn of 55%. We evaluated this group for evidence of respiratory failure (ARF) as defined by the respiratory failure index (RFI) (PaO2/FIO2 < or = 300). While only 23% of admissions to the burn center were related to flame burns, these injuries accounted for 82% of children who had ARF. Forty-two percent of these intubated children had abnormalities on their admission chest x-ray and 61% of this cohort developed evidence of ARF as defined by the RFI. The development of sepsis along with ARF regardless of TBSA involvement doubles the mortality of ARF alone. Early burn wound excision and grafting is critically important to prevent the late complication of sepsis. We carefully monitor ventilator settings to insure low peak inspiratory pressures, allowing relative hypercapnia and avoiding hyperoxia. Despite an increased number of admissions and critically injured children, we have not seen an increase in morbidity and have had a 53% reduction in mortality in the last 2 years with these techniques. We believe this management offers the best outcome for the pediatric burn victim and would recommend this strategy to other centers dealing with these severely injured children.
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PMID:Mortality and respiratory failure in a pediatric burn population. 826 96

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with the length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was determined by assay and P450 activity was determined by the metabolism of ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring malondialdehyde content. Septic rats showed decreases in P450 levels and activity, which worsened with duration of sepsis. These decreases were partially lessened by hyperoxia. Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant. This study suggests that while MFO content and activity decrease with sepsis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance.
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PMID:Mixed-function oxidase activity in sepsis. 853 82

Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] decreases lipid peroxidation in vitro and in vivo suppresses proinflammatory cytokine expression in models of lung injury due to sepsis, blood loss, and oxidative damage. In the present experiments, we used a murine hyperoxia model to examine the effects of lisofylline on the activation of nuclear transcriptional regulatory factors [nuclear factor-kappaB and cAMP response element binding protein (CREB)], the expression of proinflammatory cytokines in the lungs, and the circulating levels of oxidized free fatty acids as well as on hyperoxia-induced lung injury and mortality. Treatment with lisofylline inhibited hyperoxia-associated increases in tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in the lungs as well as decreased the levels of hyperoxia-induced serum-oxidized free fatty acids. Although hyperoxic exposure produced activation of both nuclear factor-kappaB and CREB in lung cell populations, only CREB activation was reduced in the mice treated with lisofylline. Lisofylline diminished hyperoxia-associated increases in lung wet-to-dry weight ratios and improved survival in animals exposed to hyperoxia. These results suggest that lisofylline ameliorates hyperoxia-induced lung injury and mortality through inhibiting CREB activation, membrane oxidation, and proinflammatory cytokine expression in the lungs.
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PMID:Effects of lisofylline on hyperoxia-induced lung injury. 1033 34


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