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)

Technetium-99m hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes are well established for the investigation of inflammatory disease. Their kinetics and normal distribution are similar to those of indium-111-labeled leukocytes except for nonspecific activity in urine, kidneys, gall bladder, and bowel, which results from the elution of secondary 99mTc-labeled HMPAO complexes. The principal clinical indications for [99mTc]HMPAO-leukocytes include inflammatory bowel disease (IBD), osteomyelitis, soft tissue sepsis, and, to a lesser extent, occult fever. The superior resolution and count density of 99mTc places [99mTc]HMPAO-leukocytes at an advantage over 111In-leukocytes in IBD, especially for the identification of small bowel involvement in patients with Crohn's disease. However, quantification of disease activity is more difficult than with 111In. Technetium-99m HMPAO-leukocytes are indicated for most forms of acute soft tissue and abdominal sepsis, although when compared with 111In, it may be more difficult to demonstrate communication between an abdominal abscess and bowel lumen. Chronic osteomyelitis, including infected joint prostheses, are better approached with 111In-labeled leukocytes. Occult fever and fever of unknown origin (FUO) are more controversial. There is still a place for gallium-67 in FUO, of which there is a wide spectrum of causes. Occult fever implies a pyogenic cause for an undiagnosed fever and should probably be imaged with 111In-leukocytes. With the advances being made in other imaging modalities and in interventional radiology, there is a clear need for radionuclide agents that can be used for whole-body screening in patients with undiagnosed fever. Such agents may include fluorine-18-fluorodeoxy-glucose and radiolabeled monoclonal antibodies to endothelial adhesion molecules activated at the foci of inflammation.
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PMID:The utility of [99mTc]HMPAO-leukocytes for imaging infection. 802 68

Myelosuppression is an important and potentially lethal complication of azathioprine treatment. The blood count has been reviewed in all patients treated with azathioprine for inflammatory bowel disease over 27 years in one hospital. Altogether 739 patients (422 with Crohn's disease, 284 with ulcerative colitis, and 33 with indeterminate colitis) were treated with 2 mg/kg/day azathioprine for a median of 12.5 months (range 0.5-132) between 1964 and 1991. Full blood counts were performed monthly for the duration of treatment. In 37 patients (5%) who developed bone marrow toxicity, the drug was withdrawn or the dose reduced. Thirty two of these patients were asymptomatic and five developed symptoms. Leucopenia (white blood count less than 3.0 x 10g/l) occurred in 28 (3.8%) patients, in nine of whom it was severe (white blood count < 2.0 x 10(9)/l). Of these nine patients, three were pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients with severe leucopenia developed a mild upper respiratory infection only. Thrombocytopenia (platelet count < 100,000 x 10(6)/l) in 15 patients was associated with leucopenia in six and developed in isolation in a further nine (total 2%). Isolated thrombocytopenia was never clinically severe. Myelotoxicity from azathioprine developed at any time during drug treatment (range 2 weeks-11 years after starting the drug) and occurred either suddenly or over several months. Bone marrow suppression as a result of azathioprine treatment is uncommon when a moderate dose is used, but is potentially severe. Leucopenia is the commonest and most important haematological complication. Regular monitoring of the full blood count is recommended during treatment.
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PMID:Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. 817 58

Macrophage major histocompatibility complex (MHC) class II antigen expression is associated with defective antigen presentation to T lymphocytes in animals and is predictive of patient outcome after major trauma or sepsis. In this study, class II antigen (HLA-DR and DQ) expression on peripheral blood monocytes was investigated in patients with inflammatory bowel disease in relation to disease activity and outcome. The percentage positivity and fluorescent intensity of expression of HLA-DR and DQ antigens on monocytes were determined in whole blood samples using dual colour immunofluorescence labelling and flow cytometry. Disease activity was assessed using clinical and laboratory indices. There was no significant difference in percentage positivity or fluorescent intensity of class II antigen expression between patients with Crohn's disease, those with ulcerative colitis, and healthy volunteers. The percentage of monocytes displaying HLA-DR positivity was significantly decreased in patients with active ulcerative colitis (active %: 49.5 (5.6); inactive %: 78.9 (6.9); p = 0.01). Data expressed as mean (SEM). In patients requiring surgical resection of diseased bowel, the percentage of monocytes displaying HLA-DR positivity (51.9 (4.0) %) was significantly reduced compared with patients receiving medical treatment alone (81.1 (3.5) %; p < 0.001). Reduced monocyte HLA-DR expression is therefore associated with disease activity and seems to predict outcome in patients with inflammatory bowel disease.
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PMID:Class II major histocompatibility complex antigen expression on peripheral blood monocytes in patients with inflammatory bowel disease. 817 90

Eicosanoids were discovered as "prostaglandins" in the mid-1930s. The discovery that eicosanoids were ubiquitous in mammalian cells and that nonsteroidal anti-inflammatory drugs worked by inhibiting enzymes that synthesized these chemicals heralded their extensive investigation in all fields of biology. Precursor fatty acids (arachidonic acids) are stored in cell phospholipids, acted on by two enzymes (cyclooxygenase and lipooxygenase) that yield prostaglandins, thromboxane, prostacyclin, and leukotrienes. Knowledge of their biochemical processes continue to unfold, but it is now believed that eicosanoids are part of a larger group of agents termed phospholipid mediators. Eicosanoids are intimately involved with cardiovascular function as well as central and peripheral vascular disease processes and ischemia. In the gastrointestinal tract, these potent lipids not only participate in many normal functions (eg, acid secretion and motility) but also in disease states (eg, inflammatory bowel disease and peptic ulcer disease). In shocklike states of sepsis and/or endotoxemia, eicosanoids have assumed a major role in many events that occur. Recently, discoveries have demonstrated that platelet-activating and tumor necrosis factors exert their effects in part through eicosanoids. The future will demonstrate these compounds to be critical not only in intracellular (molecular) events but also in the effects they produce that are far from the source of origin.
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PMID:Eicosanoids. Critical agents in the physiological process and cellular injury. 823 81

A controlled, randomized trial with blind assessment of end points is described comparing ceftriaxone (1 g) given at induction of anesthesia with gentamicin (2 mg/kg) and metronidazole (500 mg) (GM), three times, every eight hours starting at induction, in preventing wound, chest, and urinary tract infections following bowel operations. Patients with inflammatory bowel disease received prophylaxis for five days. Two hundred sixty patients were randomized, and 196 were studied after exclusions. Ninety-four were given ceftriaxone, and 102 were given GM. Chest infection was defined as pyrexia plus clinical or radiologic signs of consolidation or the production of purulent sputum. Wound infection was diagnosed on the basis of purulent wound discharge or pyrexia plus swelling, redness, and pain around the wound, and urinary tract infection was diagnosed from microbiologic results. There was a significant reduction in wound infection (17 percent to 6 percent; P < 0.05) and in urinary tract infection (8 percent to 1 percent; P < 0.05) in the ceftriaxone group compared with the GM group. Chest infection occurred in 16 percent of the ceftriaxone group compared with 25 percent of the GM group, but this difference was not statistically significant. Infected patients were in the hospital more than four days longer than uninfected patients, a statistically significant difference (P < 0.01). It is concluded that ceftriaxone is superior to GM in reducing postoperative sepsis and that this effect is likely to be due to the sustained bactericidal blood levels achieved by ceftriaxone.
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PMID:Ceftriaxone is more effective than gentamicin/metronidazole prophylaxis in reducing wound and urinary tract infections after bowel operations. Results of a controlled, randomized, blind clinical trial. 837 23

IL-1ra is the first described naturally occurring receptor antagonist of any cytokine or hormone-like molecule. IL-1ra is a member of the IL-1 family by three criteria: amino acid sequence homology of 26 to 30% to IL-1 beta and 19% to IL-1 alpha; similarities in gene structure; and common gene localization to human chromosome 2q14. Two structural variants of IL-1ra exist: sIL-1ra, a secretory molecule produced by monocytes, macrophages, neutrophils, fibroblasts, and other cells; and icIL-1ra, an intracellular molecule produced by keratinocytes and other epithelial cells, macrophages, and fibroblasts. IL-1ra production by monocytes, macrophages, and neutrophils may be regulated in a differential fashion with IL-1 beta. Human IL-1ra binds to both human IL-1RIs and IL-1RIIs on cell surfaces, although with 100-fold greater avidity to IL-1RIs. IL-1ra may bind preferentially to soluble IL-1RIs and not at all to soluble IL-1RIIs. IL-1ra competitively inhibits binding of both IL-1 alpha and IL-1 beta to cell surface receptors without inducing any discernible intracellular responses. All three forms of IL-1 may bind to IL-1 receptors in a similar fashion but IL-1ra may lack the secondary interactions necessary to trigger cell responses. A 100-fold or greater excess of IL-1ra over IL-1 may be necessary to inhibit biological responses to IL-1 both in vitro and in vivo. The roles of sIL-1ra and icIL-1ra in normal physiology or in host defense mechanisms remain unclear. The administration of IL-1ra blocks the effects of IL-1 in some animal models of septic shock, inflammatory arthritis, graft-versus-host disease, and inflammatory bowel disease. The preliminary results of clinical trials in humans indicate possible efficacy of IL-1ra in sepsis syndrome, rheumatoid arthritis, and GVHD.
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PMID:Interleukin-1 receptor antagonist. 837 62

Interleukin 10 (IL-10) indirectly prevents antigen-specific T-cell activation, which is associated with downregulation of the antigen presentation and accessory cell functions of monocytes, macrophages, Langerhans cells and dendritic cells. In addition, IL-10 inhibits T-cell expansion by directly inhibiting IL-2 production by these cells. These properties of IL-10, together with its capacity to downregulate the production of proinflammatory cytokines and chemokines by activated monocytes, polymorphonuclear leucocytes and eosinophils, indicate that IL-10 is a potent immunosuppressant in vitro. IL-10 has similar activities in vivo. It inhibits lipopolysaccharide or staphylococcal enterotoxin B induced lethal shock in mice. In addition, IL-10 deficient mice develop chronic inflammatory bowel disease, which could be reduced, or prevented by IL-10 treatment. IL-10 also prevented the development of colitis in a SCID mouse model. Collectively, these data indicate that IL-10 has great potential therapeutical utility in the treatment of diseases, such as chronic inflammation, autoimmune diseases, transplant rejection, graft-versus-host disease and sepsis.
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PMID:Immunosuppressive and anti-inflammatory properties of interleukin 10. 854 Oct 28

Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.
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PMID:Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. 860 44

There is growing evidence that endogenous nitric oxide (NO) regulates mucosal barrier integrity under physiological conditions and counters the increase in mucosal permeability associated with acute pathophysiological states. The potential mechanisms of action for the protective effects of NO are discussed. These include maintenance of blood flow, inhibition of platelet and leukocyte adhesion and/or aggregation within the vasculature, modulation of mast cell reactivity, and scavenging of reactive oxygen metabolites such as superoxide. On the basis of the data presented, we conclude that both constitutive nitric oxide synthase (cNOS)-derived endogenous NO and exogenous NO (from NO donors) appear to reduce the sequelae of acute inflammation. The second section of this review summarizes the data germane to prolonged (chronic) inflammatory conditions associated with the overproduction of NO from the inducible form of NOS (iNOS). Some emphasis is placed on the role of NO in sepsis and inflammatory bowel disease (IBD), and data to suggest that NO, or more specifically a NO-derived mediator, is involved in these disorders are summarized. These studies are compared with recent publications suggesting that inhibition of NO synthesis with nonspecific inhibitors of NOS or selective iNOS inhibitors may not protect in models of sepsis or IBD. Overall, the review highlights the potential importance of the type of NOS enzyme involved in the particular inflammatory process being studied.
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PMID:A critical role for nitric oxide in intestinal barrier function and dysfunction. 877 63

The analysis of the prognostic factors in patients with gastrointestinal fistula requires an assessment of the quantitative and qualitative characteristics of the study population. General patient characteristics such as age, presence and degree of malnutrition, levels of plasma proteins, diagnosis of cancer or inflammatory bowel disease, or systemic sepsis must be considered, as well as local fistula characteristics. Besides the local anatomic characteristics of the fistulous tract, other factors such as fistula output, organ of origin, cause, and duration of the fistula must be considered in the assessment of a fistula patient. It is recognized, however, that it is very difficult to conclude that the presence of a single prognostic factor increases the risk in patients as complex and heterogeneous as those with digestive fistulas. It remains to be shown whether the combination of several predictive factors may enhance the chances of accurately predicting fistula closure and mortality in digestive fistulas.
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PMID:Factors influencing outcome in patients with gastrointestinal fistula. 884 73


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