Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical course of 37 patients who underwent 46 liver transplantations for primary (n = 33) and secondary (n = 4) sclerosing cholangitis was reviewed. The median follow-up was 37 months. The patient and graft survivals for patients with primary sclerosing cholangitis at 1, 2, and 5 years were 96.9%, 91.6%, 87.9%, and 83.1%, 74.2%, 65.2%, respectively. In the patients with primary sclerosing cholangitis (PSC), prior surgery except for simple cholecystectomy was associated with significantly greater operative time and blood loss. No cholangiocarcinoma was identified at the time of transplantation. Human leukocyte antigen typing for PSC patients was heavily weighed toward B8 (58.8%) compared with control (11.8%). Sixty-two percent of patients with PSC also had inflammatory bowel disease. Moderate or severe rejection requiring OKT3, "rescue therapy" with FK506, or retransplantation was relatively higher in patients with inflammatory bowel disease (70%) versus patients without inflammatory bowel disease (36.4%) and a matched control group (37.5%). Progressive inflammatory bowel disease was seen in 6 of 19 patients, with 3 developing cancer and a dysplasia. Two patients in the entire group died of sepsis and 3 of colon cancer (2 recurrent and 1 primary). These data demonstrate that excellent survival results can be achieved in this group of patients. Rejection is frequent and often severe and steroid refractory. Colon cancer represents the most frequent cause of death in PSC patients after liver transplantation and demands constant attention.
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PMID:Liver transplantation for sclerosing cholangitis. 763 12

The diagnosis of abdominal infections and inflammations often presents considerable difficulty, and various imaging techniques may be required to localize them accurately. At present, radiolabelled leucocytes offer the most widely accepted radionuclide method for imaging inflammation. Because of the many advantages of technetium-99m (99mTc) over indium-111 (111In), 99mTc-HMPAO-leucocyte scintigraphy is preferred for the investigation of acute abdominal sepsis and inflammatory bowel disease, and 111In-leucocyte scintigraphy for more chronic infections and renal sepsis. The 99mTc-HMPAO-labelled leucocytes technique is highly accurate within the first few hours postinjection, and is therefore useful also in acutely ill patients. It is sensitive in detecting abdominal abscesses in all locations except the liver and spleen. By whole body imaging, unsuspected sites and types of infection can be found. 99mTc-HMPAO-leucocyte scan is valuable also in the investigation of acute cholecystitis in problematic situations in which ultrasound is known to give misleading results, especially in acute acalculous cholecystitis. In inflammatory bowel disease it can reliably assess disease activity, but a normal scintigraphy does not exclude mild inflammation. Leucocyte scan is useful also in suspected acute appendicitis, acute diverticulitis, pelvic inflammatory disease, aortic graft infection, etc. But infection and inflammation cannot reliably be differentiated, which may cause misinterpretations in the early postoperative period. Radionuclide techniques have an important role to play in the investigation of abdominal sepsis if the nuclear medicine department can offer instant investigations when the clinical problem is acute.
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PMID:Investigation of suspected intra-abdominal sepsis: the contribution of nuclear medicine. 797 41

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

Septicemia is the major cause of morbidity in home parenteral nutrition patients, accounting for approximately 70% of rehospitalizations. To identify risk factors, the incidence of infection was examined in 41 current home parenteral nutrition patients, 30 with short-bowel syndrome (including 16 with inflammatory bowel disease and 11 with bowel infarction) and 11 with chronic obstructive disorders. Management, which was followed for a mean duration of 78.6 months (range, 1 to 15 1/2 years), was standardized by protocol. Ten patients never experienced infection during the average follow-up of 61 months (range, 14 to 174 months), whereas seven patients experienced frequent infections during the mean follow-up of 77 months (range, 24 to 180 months). Significant distinguishing features in the frequent-infection group were younger age (45 +/- 12 vs 66.9 +/- 14.3 years, p < .05), Crohn's disease (in five of seven vs zero of 10 subjects, p < .05), jejunostomies (in seven of seven vs one of 10 subjects, p < .0005), and central vein thrombosis (in five of seven vs zero of 10 subjects, p < .05). A greater proportion of the frequent-infection group had poor catheter-care technique and more were smokers. One hundred fifty septicemias were confirmed by blood culture, giving an average infection rate of one every 31 months, 52% caused by Gram-positive organisms (chiefly coagulase-negative staphylococci and Staphylococcus aureus), 30% caused by Gram-negative organisms, and 16% caused by fungus (chiefly Candida albicans).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recurrent sepsis in home parenteral nutrition patients: an analysis of risk factors. 806 2

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


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