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)

Between November 1996 and November 1997 we have transplanted 13 patients with Cystic Fibrosis (CF). Bilateral Sequential Lung Transplantation (BSLT) was successfully performed in all patients; one patient died from pneumonia and sepsis in the postoperative period and 12 are alive and well after a follow-up ranging between 1 and 13 months. Blood gas analysis improved from mean values of PaO2: 56 mm/Hg (with oxygen) and PaCO2: 43 mm/Hg to mean values of PaO2: 85 mm/Hg and PaCO2: 37 mm/Hg. Pulmonary function tests also improved dramatically: FEV1 improved from 20% predicted to 98% predicted. FVC also improved from 39% to 100%. The quality of life markedly improved: the ideal body weight moved from about 84% to normal values within nine months, and the 6-minute walk-test improved after transplantation from a preoperative distance of 325 meters, to 600 meters after 6 months. In conclusion, our favorable experience with BSLT in CF patients emphasizes the importance of lung transplantation in these patients. Carefully selected and properly managed patients may benefit from transplantation in terms of quality and duration of life.
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PMID:Lung transplantation for cystic fibrosis. 978 42

Whole cells and lipopolysaccharides (LPSs) extracted from Burkholderia cepacia, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Escherichia coli were compared in their ability to stimulate tumor necrosis factor alpha (TNF-alpha) from the human monocyte cell line MonoMac-6. B. cepacia LPS, on a weight-for-weight basis, was found to have TNF-alpha-inducing activity similar to that of LPS from E. coli, which was approximately four- and eightfold greater than the activity of LPSs from P. aeruginosa and S. maltophilia, respectively. The LPS-stimulated TNF-alpha production from monocytes was found to be CD14 dependent. These results suggest that B. cepacia LPS might play a role in the pathogenesis of inflammatory lung disease in cystic fibrosis, and in some patients it might be responsible, at least in part, for the sepsis-like cepacia syndrome.
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PMID:Lipopolysaccharide (LPS) from Burkholderia cepacia is more active than LPS from Pseudomonas aeruginosa and Stenotrophomonas maltophilia in stimulating tumor necrosis factor alpha from human monocytes. 1002 1

Nitric oxide (NO) is produced from three isoforms of nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS). Cystic fibrosis (CF) patients have an increased bacterial load in the airways which stimulates iNOS and therefore NO production. Upregulation of iNOS in normal epithelial cells protects the lung from damage, but in CF cells, iNOS is not upregulated and NO production is reduced. Reduced iNOS expression is associated with neutrophil sequestration in the lung, thus increasing the potential damage from neutrophil proteases and reactive oxygen species. In contrast, high concentrations of NO may augment the inflammatory process in acute lung injury from sepsis. Meng et al. have shown that cystic fibrosis epithelial cells, when stimulated by a cytokine mix and co-cultured with activated neutrophils, have reduced iNOS expression compared to normal epithelial cells. Although iNOS expression may not accurately reflect activity and NO production may arise from elsewhere, this study suggests that reduced iNOS expression may play a part in the pathophysiological processes in cystic fibrosis.
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PMID:Nitric oxide, iNOS, and inflammation in cystic fibrosis. 1065 9

Pseudomonas aeruginosa plays a major role in respiratory tract infections or sepsis in patients with cystic fibrosis or upon suppression of the immune system. Several P. aeruginosa strains have been shown to be internalized by human epithelial cells; however, the molecular mechanisms of the invasion process are poorly characterized. Here, we show that the internalization of P. aeruginosa into human epithelial cells results in and requires activation of the Src-like tyrosine kinases p59Fyn and p60Src and the consequent tyrosine phosphorylation of several eukaryotic proteins. The significance of Src-like tyrosine kinase activation is shown by an almost complete blockade of P. aeruginosa internalization, but not adhesion, upon inhibition of Src-like tyrosine kinases. Likewise, inhibition of P. aeruginosa binding to CFTR, which has been shown to block P. aeruginosa internalization, prevents Src and Fyn activation, supporting a pivotal role of Src-like tyrosine kinases for invasion by P. aeruginosa.
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PMID:Invasion of human epithelial cells by Pseudomonas aeruginosa involves src-like tyrosine kinases p60Src and p59Fyn. 1111 16

Cystic fibrosis is a congenital disease resulting from an abnormality of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A defect in ion transport leads to poor clearance of viscoelastic secretions and a susceptibility to bacterial infection. This initiates a self-perpetuating cycle of infection and inflammation that accounts for the chronic endobronchial sepsis and pulmonary damage observed in patients with cystic fibrosis. Recent studies have attempted to correct the gene defect, enhance the expression and function of the CFTR protein and correct the ion transport defect. Improving the rheological properties of airway secretions, enhancing host defence and controlling inflammation are the other key strategies.
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PMID:Update on clinical trials in the treatment of pulmonary disease in patients with cystic fibrosis. 1113 34

Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.
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PMID:Misoprostol therapeutics revisited. 1119 38

Leptin, a cytokine involved in the regulation of food intake, has been reported to be decreased in lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis and increased in critically ill patients with sepsis. We investigated the role of leptin during hyperoxia in mice, which results in alveolar edema, severe weight loss, and death within 3-4 days. In oxygen-breathing mice, serum leptin was increased six- to sevenfold and its mRNA was upregulated in white adipose tissue. Leptin elevation could not be attributed to changes in circulating tumor necrosis factor-alpha but was completely dependent on endogenous corticosterone elevation because adrenalectomized mice did not exhibit any increase in leptin levels. Using leptin-deficient mice and wild-type mice treated with anti-leptin antibody, we demonstrate that weight loss was leptin independent. Lung damage was moderately attenuated in leptin-deficient mice but was not modified by anti-leptin antibody or leptin administration, suggesting that leptin does not play an essential role in the direct and short-term effects of oxygen-induced injury.
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PMID:Hyperoxia increases leptin production: a mechanism mediated through endogenous elevation of corticosterone. 1159 6

The spectrum of surgical diseases in patients with cystic fibrosis (CF) has not been comprehensively studied. A retrospective review of 792 consecutive patients with CF presenting over a 25 year period (1970-1994) was made to determine the incidence of operations, procedures performed, complications encountered, and impact on physical development and pulmonary function tests (PFTs). A total of 191 operations were performed on 130 (16%) of the 792 patients; 98 operations (51%) were abdominal, 58 (30%) thoracic, and 31 (16%) hernias; 64 were male, and 66 female; average age was 14 +/- 10 years. Complications occurred in 12 (16%); 9 deaths were from progressive respiratory failure, 2 from superficial wound infections, and 1 from an episode of line sepsis. In the first 15 years, 9 complications occurred in 126 operations vs. 3 in 73 operations during the last 10 years. Operations were classified as emergent, urgent, or elective. Of the 9 deaths, 8 occurred after emergent or urgent operations (4 abdominal and 4 thoracic), while 1 death occurred following elective herniorrhaphy. For each subgroup, (abdominal, thoracic, and hernia), there was no difference in height/weight indicies, peak flow, forced vital capacity (FVC), forced expired volume in 1 sec (FEV(1)), or FEV(1)/FVC ratio when comparing 1 year preoperation and 1 year postoperation. In conclusion, patients in this high-risk population were operated on with few complications, but when a complication occurred it tended to be pulmonary and fatal (4.7% of all operations). Furthermore, operations did not cause significant deteriorations in PFTs and they did not cause these children to fall off their expected age-adjusted growth curves.
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PMID:Surgical experience in patients with cystic fibrosis: a 25-year perspective. 1180 46

Gram-negative infections can cause overwhelming inflammatory responses. Although factors other than LPS are clearly involved, these factors and their mechanisms of action have been poorly defined. During studies of LPS-independent inflammatory responses of the gram-negative pathogen Pseudomonas aeruginosa, an important virulence factor (exoenzyme S) was shown to be a potent mitogen for T cells. The current work demonstrates that exoenzyme S selectively induced transcription and secretion of biologically active cytokines and chemokines (chemotactic for neutrophils and T cells) from monocytes. Exoenzyme S stimulated highly purified monocytes independent of T cells. In addition, exoenzyme S stimulated T cells directly; neither T-cell activation (CD69) nor apoptosis (hypodiploidy) required the presence of monocytes. However, T-cell activation was enhanced via a noncontact-dependent mechanism as a result of the secretion of TNF-alpha and IL-6. This study identifies a unique property of a gram-negative-derived microbial product capable of activating multiple cell types and suggests a mechanism by which exoenzyme S contributes to the immunopathogenesis of cystic fibrosis and sepsis in patients infected with P. aeruginosa.
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PMID:Distinct fates of monocytes and T cells directly activated by Pseudomonas aeruginosa exoenzyme S. 1186 83

The objective of this study was to characterize, and determine the significance of, pulmonary activity on labelled leukocyte images. This retrospective review included 137 immunocompetent patients who had undergone 111In labelled autologous leukocyte chest imaging and chest X-ray within 7 days. Pulmonary activity was classified as normal, focally increased, or diffusely increased. Images were correlated with chest X-rays and final diagnoses. One hundred and twelve patients (82%) had normal pulmonary activity. Seventy-six had normal chest X-rays; none had pulmonary infection. Thirty-six patients had chest X-ray abnormalities; only one had pulmonary infection. Twenty-five patients had abnormal pulmonary activity. In 13 patients it was segmental or lobar in distribution. The chest X-ray was abnormal in 12: pneumonia (11) and cystic fibrosis (one). The chest X-ray was normal in one patient with pneumonia. Two patients with non-segmental pulmonary activity did not have pulmonary infection. The chest X-ray was abnormal in one (pulmonary edema) and normal in one (sepsis). Ten patients had diffuse pulmonary activity. Chest X-ray was abnormal in two patients: adult respiratory distress syndrome (ARDS) (one) and drug toxicity (one). No patient with diffuse pulmonary activity had pulmonary infection. In summary, negative labelled leukocyte imaging excludes pulmonary infection with a high degree of certainty (the negative predictive value was 99% in this series), and can exclude pneumonia as the cause of a chest X-ray abnormality. Focal pulmonary activity strongly suggests pneumonia, while diffuse pulmonary activity is unlikely to indicate infection.
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PMID:Pulmonary activity on labelled leukocyte images: patterns of uptake and their significance. 1202 11


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