Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There were 1,536 lung transplants reported to the St. Louis International Lung Transplant Registry as of September 1, 1992. The number of centers performing lung transplants increased each year. The 1- and 2-year actuarial survival statistics for all transplants were 68% and 60%, respectively. The most common indication for transplantation was chronic obstructive pulmonary disease, followed by idiopathic pulmonary fibrosis, emphysema secondary to alpha-1 antitrypsin deficiency, and cystic fibrosis. Among the total of 492 deaths reported (34%), sepsis was the leading cause of death.
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PMID:Current status of lung transplantation--report of the St. Louis International Lung Transplant Registry. 130 24

Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (Interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN). Increased expression of IL-8 has been described in other inflammatory disorders characterized by neutrophilic infiltration, including psoriasis, rheumatoid arthritis, and the sepsis syndrome, but no studies have assessed this cytokine in the context of interstitial pulmonary disorders. We have previously shown that normal human AM release IL-8 upon appropriate stimulation, but data assessing the expression of IL-8 by human AM in specific pulmonary disease states are lacking. In this study, we examined the expression of steady-state mRNA for IL-8 by human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis and from healthy volunteers. Because it is known that adherence to plastic culture plates may up-regulate gene expression for IL-8 in the absence of additional stimulation, we extracted mRNA immediately from the cell pellet obtained by BAL rather than using cultured alveolar macrophage monolayers. Northern blot analysis was performed to determine IL-8 mRNA expression. We found that BAL cells from patients with IPF constitutively expressed mRNA for IL-8, and the amount of IL-8 mRNA (as assessed by laser densitometry) correlated with the percent of neutrophils on BAL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophilic alveolitis in idiopathic pulmonary fibrosis. The role of interleukin-8. 159 15

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.
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PMID:Angiotensin converting enzyme in bronchoalveolar lavage in ARDS. 302 28

Clinical studies of ARDS have been successful in determining the most common predisposing clinical disorders and the natural history of this syndrome. Sepsis, gastric aspiration, and major trauma are the most frequently associated high-risk factors. Overall mortality is in the range of 60% to 70%, but is even higher if ARDS is associated with sepsis, severe acidemia, or decreased renal function. It is evident that multisystem failure is responsible for death in many patients, as well as secondary pulmonary and extrapulmonary infections. Pathologic studies have provided descriptive information regarding the acute, subacute, and chronic phases of the syndrome, but little insight into the precise pathogenesis of the initial lung injury or the progressive fibrosing alveolitis and lung destruction that develops in some patients. There has been considerable circumstantial evidence from clinical studies implicating the neutrophil as a potentially important mediator of the early changes in lung endothelial and epithelial permeability. However, not all investigators have found the same alterations in neutrophil function in the circulation or in the lavage from the lungs of patients with ARDS. Also, the heterogeneous etiologies of ARDS make it difficult to be sure that there is a final common pathway for acute lung injury in all ARDS patients. In addition, there are a host of mediators, including products of complement activation and arachidonic acid metabolism, that may be important in amplifying the inflammatory response. Also, abnormalities of surfactant production and collagen turnover, as well as impaired host defenses in the lung, may contribute to the progressive respiratory failure that occurs in some ARDS patients, even though the acute, exudative phase of lung injury has resolved. Future human studies may provide useful information about the mechanisms of the acute lung injury through studies of circulating plasma markers, blood elements, and lavage fluids from high-risk patients. On the other hand, samples of cells and mediators from the airspaces with lavage still may not reflect the critical interactions of mediators and cells with the lung endothelium that lead to the protein-rich pulmonary edema that characterizes the first phase of ARDS. Thus, experimental studies must continue to study the details of the early phases of acute lung injury (see article by Flick, page 455). Finally, it is clear that treatment designed to reduce the severity and the incidence of ARDS must be started early, since the syndrome develops so rapidly in high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathophysiology of the adult respiratory distress syndrome. What have we learned from human studies? 333 57

Cardiopulmonary resuscitation was successful in a healthy 29-year-old woman who had been submerged for 20 minutes in water at 10 degrees C. The evolution was characterized by the development of a multifactorial ARDS (secondary drowning) and sepsis caused by Aeromonas hydrophila and Acinetobacter anitratum. Fibrosing alveolitis caused a restrictive syndrome with severe mechanical impairment and transitory therapy-resistant hypoxemia. It is suggested that prolonged submersion in cold water is also a treatable and completely reversible condition in adults. In our patient without neurological sequelae the pulmonary function studies after 3 months show complete recovery from the mechanical impairment. After a follow-up period of 11 months only mild abnormalities of gas exchange persist.
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PMID:[Near-drowning in an adult: favorable course after a 20-minute submersion]. 628 69

A number of adhesion molecules on neutrophils and the pulmonary capillary endothelium mediate the neutrophil accumulation in the lungs at the onset of adult respiratory distress syndrome or acute lung injury (ALI). P-selectin, located on both vascular endothelial cells and platelets, has been shown to be one of these neutrophil-endothelial cell adhesion molecules. In this study, we measured the soluble form of P-selectin in plasma (PPS) from 19 patients (surviving, 11; deceased, 8) with ALI due to various causes and assessed the clinical significance of this measurement. Twelve healthy subjects and 29 patients with other pulmonary diseases, including idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 5), pneumonia (n = 8), and sepsis without ALI (n = 8) were also studied for comparison. PPS in patients with ALI (474.5 +/- 366.8 ng/ml, mean +/- SD) were significantly higher than those in control subjects (98.8 +/- 39.7, p < 0.01) and in patients with IPF (210.4 +/- 76.6, p < 0.05), sarcoidosis (135.2 +/- 71.5, p < 0.05), pneumonia (225.3 +/- 81.0, p < 0.05), and sepsis without ALI (271.8 +/- 46.5, p < 0.05). There was no significant difference in PPS levels between seven patients with and 12 patients without multiple organ failure. Lung injury scores correlated significantly with the PPS level (r = 0.605, p < 0.05). PPS levels of deceased patients with ALI (841.0 +/- 252.4) were significantly higher than those of surviving patients with ALI (208.0 +/- 109.2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Soluble form of P-selectin in plasma is elevated in acute lung injury. 753 27

Macrophage inflammatory proteins 1 alpha and beta (MIP-1 alpha and beta) and macrophage inflammatory protein 2 (MIP-2) are approximately 6-8 kd, heparin binding proteins that exhibit a number of inflammatory and immunoregulatory activities. The MIP proteins are members of a superfamily of cytokines called chemokines, many of which have been shown to possess chemotactic activity for inflammatory and immune effector cells. While MIPs were originally identified as secretory products of endotoxin-stimulated mouse macrophages, these chemokines are produced by a variety of cell types including neutrophils, fibroblasts, and epithelial cells. In addition, proteins with a high degree of structural and functional homology to murine MIP-1 alpha and beta and MIP-2 have been identified in other species including humans. MIP-1 alpha and beta are chemotactic for monocytes and lymphocytes and MIP-2 is a potent chemotactic factor for neutrophils. MIPs likely also play a role in regulating hematopoiesis and stimulating production of other inflammatory mediators such as IL-1, TNF alpha, and histamine. Studies using animal models of lung injury and inflammation have implicated MIPs as important mediators of lung defense. Increased MIP expression has been observed in models of bacterial sepsis, silicosis, and oxidant-induced lung injury. Studies in humans indicate MIP-1 alpha contributes to the inflammatory cell response associated with sarcoidosis and idiopathic pulmonary fibrosis. Given the bioactivities of MIP-1 alpha and beta and MIP-2 and the recent studies demonstrating their association with lung inflammation, it is likely these chemokines play a significant role in respiratory tract defenses and may contribute to the pathogenesis of inflammatory lung disease.
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PMID:Macrophage inflammatory proteins: biology and role in pulmonary inflammation. 788 2

Of the 120 systemic lupus erythematosus (SLE) patients treated by the authors, two have developed diffuse alveolar haemorrhage. The authors' objective is to present this rare, but severe manifestation. Patients 1 and 2 were 66- and 22-year old women, respectively. Both had SLE with multi-organ involvements including diffuse proliferative lupus nephritis. Before the diagnosis of the disease, both patients had experienced pneumonitis that resolved on corticosteroid treatment. Soon after the diagnosis, respiratory failure, haemoptoea and acute anaemia developed, accompanied by a rapid deterioration in the general condition. Chest radiographs revealed bilateral, diffuse, alveolar infiltrates. The pulmonary haemorrhage temporarily ceased in response to corticosteroid treatment, but both patients later died in consequence of active SLE and mixed bacterial and fungal sepsis. Post mortem examination demonstrated fibrosing alveolitis and alveolar bleeding in Patient 1, and an immune complex deposition-induced alveolocapillary inflammation with alveolar haemorrhage in Patient 2. Diffuse alveolar haemorrhage is a life-threatening manifestation of SLE. Its onset may be preceded by episodes of pneumonitis resolving on corticosteroid treatment. An active diagnostic workup, intensive observation and aggressive immunosuppressive treatment are the cornerstones of the management. The early detection and the active treatment of secondary infections are obligatory. The authors consider the most difficult challenge to be the optimum coordination of the above treatment modalities.
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PMID:[Diffuse alveolar hemorrhage in systemic lupus erythematosus]. 1069 87

This retrospective study describes the clinical course of 38 patients with idiopathic pulmonary fibrosis (IPF) admitted to the intensive care unit (ICU). There were 25 males and 13 females who were the mean age of 68.3 +/- 11.5 years. Twenty patients were on corticosteroids at the time of admission to the hospital, and 24 had been on home oxygen therapy. The most common reason for ICU admission was respiratory failure. The Acute Physiology and Chronic Health Evaluation III-predicted ICU and hospital mortality rates were 12% and 26%, whereas the actual ICU and hospital mortality rates were 45% and 61%, respectively. We did not find significant differences in pulmonary function or echocardiogram findings between survivors and nonsurvivors. Mechanical ventilation was used in 19 patients (50%). Sepsis developed in nine patients. Multiple organ failure developed in 14% of the survivors and in 43% of the nonsurvivors (p = 0.14). Ninety-two percent of the hospital survivors died at a median of 2 months after discharge. These findings suggest that patients with IPF admitted to the ICU have poor short- and long-term prognosis. Patients with IPF and their families should be informed about the overall outlook when they make decisions about life support and ICU care.
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PMID:Outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive care unit. 1279 57

Nitric oxide (NO) is a potent signaling molecule that needs to be tightly regulated to maintain metabolic and cardiovascular homeostasis. The nitric oxide synthase (NOS)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is central to this regulation. Specifically, the small-molecule ADMA competitively inhibits NOS, thus lowering NO levels. The majority of ADMA is physiologically metabolized by DDAH, thus maintaining NO levels at a physiological concentration. However, under pathophysiological conditions, DDAH activity is impaired, in part as a result of its sensitivity to oxidative stress. Therefore, the application of high-throughput chemical screening for the discovery of small molecules that could restore or enhance DDAH activity might have significant potential in treating metabolic and vascular diseases characterized by reduced NO levels, including atherosclerosis, hypertension, and insulin resistance. By contrast, excessive generation of NO (primarily driven by inducible NOS) could play a role in idiopathic pulmonary fibrosis, sepsis, migraine headaches, and some types of cancer. In these conditions, small molecules that inhibit DDAH activity might be therapeutically useful. Here, we describe optimization and validation of a highly reproducible and robust assay successfully used in a high-throughput screen for DDAH modulators.
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PMID:Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high-throughput chemical screening. 2246 Jan 74


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