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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in immunocompromised patients. In immunocompetent individuals, the infection is usually subclinical but it can sometimes be life threatening. We describe a case of fatal CMV proctitis in a 71-year-old man following an Ivor-Lewis esophagectomy. After surgery he developed renal failure, methicillin-resistant Staphylococcus aureus pneumonia, and acute respiratory distress syndrome. He recovered but developed melena and massive fresh rectal bleeding. Sigmoidoscopy revealed severe proctitis and a biopsy was consistent with ischemia. Despite undergoing a proctectomy he continued to bleed and died despite every effort. The final histological examination of the rectum revealed a CMV infection.
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PMID:Severe proctitis, perforation, and fatal rectal bleeding secondary to cytomegalovirus in an immunocompetent patient: report of a case. 1718 50

The authors describe a new extracorporeal pumpless interventional lung assist system (iLA) that was implemented in two US soldiers with severe acute respiratory distress syndrome received from enemy action in Iraq, who were at risk for critical hypoxemia/hypercapnia. The system is characterized by a new low-resistance gas exchange membrane that is integrated in an arterial-venous bypass established by cannulation of the femoral artery and vein. Cardiovascular stability is essential to produce sufficiently high blood flow rates over the gas exchange unit. After implantation of the interventional lung assist, oxygenation increased and carbon dioxide elimination improved rapidly. Ventilator settings were able to be adjusted to the decreased pulmonary gas exchange needs, making protective lung strategies possible. Air transport of both patients with the running iLA system was uneventful. The iLA was removed after 15 and 8 days of continuous operation, respectively, and both soldiers were successfully weaned from mechanical ventilation. Interventional, extracorporeal pump-free pulmonary support opens up new possibilities for pulmonary protection due to ease of use, effectiveness, and low costs; however, there is concern of distal limb ischemia. Experiences to date are encouraging, although randomized studies are lacking, and the procedure carries significant risks.
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PMID:From Baghdad to Germany: use of a new pumpless extracorporeal lung assist system in two severely injured US soldiers. 1751 12

Most acute respiratory distress syndrome studies have been focused on the lung injury. Little is known about other organs during the development of acute respiratory distress syndrome. Herein, we investigated the injury and cell death in multiple organs after intestinal ischemia-reperfusion (IIR) in C57BL/6 mice. Terminal transferase dUTP nick end labeling staining was used as a marker of cell death. Caspase 3 and cathepsin B activation as markers of caspase-dependent and caspase-independent apoptosis, respectively, and electron microscopy for ultimate characterization of cell death were used. In comparison with control and sham-operated mice, the IIR group showed interstitial inflammatory infiltrates in the lung and significant increases of lung injury parameters and plasma lactate dehydrogenase and aspartate aminotransferase levels. Terminal transferase dUTP nick end labeling-positive cells and immunostaining for hemeoxygenase 1, an enzyme induced by inflammatory stimuli, were increased in the lung, heart, and kidney, but not in the liver. The number of hemeoxygenase 1-positive cells positively and significantly correlated to the number of terminal transferase dUTP nick end labeling-positive cells. Cell death was not associated with caspase 3 or cathepsin B activation. Electron microscopy showed morphological features compatible with oncotic rather than apoptotic cell death or necrosis, including mitochondrial swelling and cytoplasm disorganization in pulmonary and renal epithelial cells, lung and cardiac endothelial cells, and myocytes. These results indicate that, although lung injury is the most significant manifestation after IIR, oncotic cell death occurs in the lung, heart, and kidney, which may be related to ischemia and inflammation.
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PMID:Intestinal ischemia-reperfusion-induced acute lung injury and oncotic cell death in multiple organs. 1766 44

Paraplegia is a rare complication of surgery for acute type A aortic dissection. We report a case of delayed postoperative paraplegia associated with necrosis of the thoracic vertebral bodies and soft tissue. The pathogenesis of delayed postoperative paraplegia is unknown, but our case report would strongly suggest ischemia of the descending thoracic intercostal arteries as the causative mechanism. The precipitating episode (respiratory distress syndrome with hemodynamic instability) might have promoted the compromised spinal circulation to become clinically evident in our patient. Treatment for this serious complication is mostly supportive, although CSF drainage may be helpful in the acute phase.
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PMID:Delayed paraplegia associated with vertebral necrosis after type A dissection surgery. 1805 32

Apoptosis has been considered as an underlying mechanism in acute lung injury/acute respiratory distress syndrome and multiorgan dysfunction syndrome. Recently, several alternative pathways for cell death (such as caspase-independent cell death, oncosis, and autophagy) have been discovered. Evidence of these pathways in the pathogenesis of acute lung injury has also come into light. In this article, we briefly introduce cell death pathways and then focus on studies related to lung injury. The different types of cell death that occur and the underlying mechanisms utilized depend on both experimental and clinical conditions. Lipopolysaccharide-induced acute lung injury is associated with apoptosis via Fas/Fas ligand mechanisms. Hyperoxia and ischemia-reperfusion injury generate reactive oxidative species, which induce complex cell death patterns composed of apoptosis, oncosis, and necrosis. Prolonged overexpression of inflammatory mediators results in increased production and activation of proteases, especially cathepsins. Activation and resistance to death of neutrophils also plays an important role in promoting parenchymal cell death. Knowledge of the coexisting multiple cell death pathways and awareness of the pharmacological inhibitors targeting different proteases critical to cell death may lead to the development of novel therapies for acute lung injury.
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PMID:Acute lung injury and cell death: how many ways can cells die? 1820 16

Complement activation has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury, acute respiratory distress syndrome, and acute transplant rejection. Even though the complement cascade provides several protein targets for potential therapeutic intervention only two complement inhibitors have been approved so far for clinical use including anti-C5 antibodies for the treatment of paroxysmal nocturnal hemoglobinuria and purified C1-esterase inhibitor replacement therapy for the control of hereditary angioedema flares. In the present study, optimization of potency and physicochemical properties of a series of thiophene amidine-based C1s inhibitors with potential utility as intravenous agents for the inhibition of the classical pathway of complement is described.
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PMID:Biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s. 1824 91

As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis.
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PMID:Disruption of iron homeostasis and lung disease. 1910 Mar 11

Lung ischemia-reperfusion (IR) injury causes alveolar, epithelial and endothelial cell dysfunction which often results in decreased alveolar perfusion, characteristic of an acute respiratory distress syndrome. Nitric oxide (NO) from endothelium-derived NO synthase (eNOS) helps maintain a low pulmonary vascular resistance. Paradoxically, during acute lung injury, overproduction of NO via inducible NO synthase (iNOS) and oxidative stress lead to reactive oxygen and nitrogen species (ROS and RNS) formation and vascular dysfunction. RNS potentiate vascular and cellular injury by oxidation, by decreasing NO bioavailability, and by regulating NOS isoforms. RNS potentiate their own production by uncoupling NO production through eNOS by oxidation and disruption of Akt-mediated phosphorylation of eNOS. This review focuses on effects of NO which cause vascular dysfunction in the unique environment of the lung and presents a hypothesis for interplay between eNOS and iNOS activation with implications for development of new strategies to treat vascular dysfunction associated with IR.
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PMID:Differential effects of nitric oxide synthesis on pulmonary vascular function during lung ischemia-reperfusion injury. 1926 81

Phospholipase A(2)s (PLA(2)s) produce free fatty acid and lysophospholipid from membrane phospholipid, and these products can be converted into various types of proinflammatory lipid mediators by specific enzymes. Among several types of PLA(2), secretory PLA(2)s (sPLA(2)s) have crucial roles in the development of cardiovascular diseases. Circulating sPLA(2) is increasing in patients with coronary artery disease (CAD), and it can be a risk factor for CAD and a prognostic factor in those patients. Secretory PLA(2)s amplify the inflammatory responses in myocardial ischemia/reperfusion injury and fetal acute respiratory distress. In some animal experiments, sPLA(2)s can hydrolyze low-density lipoprotein and high-density lipoprotein and lead to progress of atherosclerotic plaques. Some inhibitor studies for sPLA(2) revealed that inhibition of sPLA(2) reduced the myocardial impairment after ischemia/reperfusion injury and progression of atherosclerotic plaque areas in animal models. Secretory PLA(2)s might be a new target for cardiovascular medicine.
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PMID:Novel insights of secretory phospholipase a(2) action in cardiology. 1967 67

When a tissue becomes ischemic, a host of changes occur at the cellular level that lead to a shift in transcriptional activity of many inflammatory and cytoprotective compounds, a process which is extensively controlled through a family of transcription factors known as nuclear factor kappa-B (NF-kappaB). This shift in activity paradoxically results in both a cytoprotective effect at the cellular level and upon reperfusion, a generally destructive inflammatory response, a phenomenon referred to as ischemia reperfusion (IR) injury. To date, a number of methods of modifying the activity of NF-kappaB through either physiologic or pharmacologic manipulation have been developed and studied in animal models of IR injury and in some cases in human clinical trials. Nearly every method of NF-kappaB antagonism has demonstrated a discrete protective effect allowing investigators to reduce myocardial infarct sizes by 60% and cerebral infarct sizes by 57% relative to untreated control animals. The problem of IR injury is all too common and represents a discrete threat not only to the tissues directly involved in the ischemic event, but also to distal sites as well as is seen in the evolution of acute respiratory distress and severe inflammatory response syndromes. In the course of this review, the nature of NF-kappaB and its involvement in IR injury is examined along with the efficacy of the various NF-kappaB-based investigational treatment developed to date.
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PMID:Searching for NF-kappaB-based treatments of ischemia reperfusion injury. 1984 7


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