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)

Ciprofloxacin is the most potent post-marketing fluoroquinolone. In vitro activity and pharmacokinetic properties of this agent, together with clinical trials of the drug may be very promising in the treatment of severe infections, especially when the bacteria involved are resistant to other conventional agents. We performed an open clinical trial of this agent in hospitalized patients with severe infections in a university hospital in Bangkok, Thailand. A total of 25 patients were enrolled on the basis of clinical diagnosis of severe bacterial infections. Six of these patients were dropouts (3 of which proved to be non-bacterial infections, 2 patients each had only anaerobic infection and nocardiosis. One suffered from a severe psychotic attack). The remaining 19 patients were evaluated. There were 12 males and 7 females, the age ranged from 13 to 77 years old (43.2 +/- 20.1). Most had severe underlying illnesses (17 out of 19). There were 23 infections in 19 patients. Septicemia was the most common infection treated. Other infections included complicated urinary infection, upper respiratory tract infection, skin/skin structure infection. P. aeruginosa was the most common pathogen infected. Other organisms were E.coli, Enterobacter, P.mirabilis, S.aureus, A.antitratus and mycobacterium. Ciprofloxacin was given as an initial 100 mg twice daily as intravenous infusion, and this was switched to an oral form of 500 mg b.i.d./at approximately day 4 to day 6. The overall cure rate was 68 per cent. There were 2 improvements, 2 relapses/reinfections and one failure. Toxic effect included one psychotic attack necessitating discontinuation of the drug. Other adverse drug reactions were mild and transient. These included elevation of transaminase and LDH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ciprofloxacin in severe infections. 223 Jun 26

Twenty-four episodes of bacterial infections were identified over a 18 month period in 11 patients (8 with acquired immunodeficiency syndrome and 3 with AIDS related complex). Eight of the 11 infected patients were drug abusers and 3 homosexual people. Nosocomial bacterial infections were common in patients with AIDS and had high fatality rates. Gram-negative bacteria resulted the most common micro-organisms (E.coli, Proteus, Enterobacter, Serratia, Klebsiella). The Aztreonam treatment was very useful in providing bacteria eradication. Gram-positive bacteria as Staphylococcus from a sepsis and Enterococcus from a cystopyelitis were eradicated by B-lactam antibiotics. Common micro-organism are frequent in patients affected by LAS/ARC or AIDS and they negatively interfere with the disease outcome.
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PMID:[Significant bacteriological findings in HIV-positive patients]. 249 36

Septicemia was induced in cats by infusion of live E. coli bacteria into the inferior vena cava, the portal vein or the aortic arch. Systemic arterial blood pressure, aortic blood flow, pulmonary arterial blood pressure, intestinal blood flow and portal venous pressure were recorded continuously and arterial platelet and white blood cell counts and acid-base balance measured at intervals. Infusion of E.coli into the inferior vena cava induced an initial response characterized by systemic pressure reduction, unchanged or increased aortic blood flow and pulmonary hypertension. Intestinal blood flow decreased moderately, while portal pressure remained unchanged. The arterial infusion evoked a similar response. After portal infusion there was a more pronounced increase of aortic blood flow, a significantly less elevation of the pulmonary artery pressure, and the intestinal blood flow was maintained. The changes induced in arterial acid-base balance or in platelet and white cell counts were not influenced by the route of administration. It is concluded that the route of administration of bacteria is of importance when considering the relevance of experimental data to clinical septic states.
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PMID:Pulmonary vascular reactions in experimental septicemia, A preliminary report. 700 84

Endotoxin(lipopolysaccharide = LPS), cell wall component of gram-negative bacteria, activates monocytes and macrophages to release cytokines, reactive nitrogen intermediates (RNI), and to generate tissue factor(TF) which initiate coagulation. We have purified 7kDa and 18kDa cationic antibacterial proteins (CAP-7 and CAP-18) with LPS-binding and LPS-neutralizing activities from rabbit granulocytes using as an assay the agglutination of erythrocytes coated with Re-LPS. From protein sequencing, CAP-7 was identified as the C-terminal 37 amino acid fragment of CAP-18. Synthetic peptide #197 (identical sequence to CAP-7, Gly1-Try37) and #36-1 (a truncation of CAP consisting of 32 amino acid residues, Gly1-Ala32) showed LPS-binding activity. Each peptide inhibited LPS-induced tissue factor(TF) generation by murine peritoneal macrophages, even added 1-3 hours after stimulation of cells with LPS. C57BL/6 mice treated with #197 were significantly protected from lethal LPS challenge. Peptide #36 also blocked the LPS-induced lethality. These peptides had antibacterial activity to gram-negative bacteria, such as E.coli, S.typhimurium, K.pneumonia, Ps.aeruginosa and also to gram-positive S.aureus (Methicillin sensitive and resistant strains). Both peptides inhibited TF- and Xa-induced plasma clotting. Using synthetic chromotogenic substrates, both CAP7 peptides blocked the coagulation cascade at two sites, activation of factor X to Xa and conversion of Factor II (prothrombin) to factor IIa (thrombin). In vivo treatment of peptide #197 prevented acute lethality in mice injected with tissue factor (rabbit brain thromboplastin). Two other peptides, #32(Gly1-Phe9) and #50(Ile13-Typ37) failed to demonstrate LPS-binding, LPS-neutralizing, antibacterial and anticoagulant activities. The active peptides but not the inactive peptide maintain a putative heparin binding domain at their N-termini. This heparin binding domain is participate in the LPS-binding, LPS neutralizing, antibacterial and anticoagulant activities of CAP7. These active peptides may have a therapeutic potential for treatment for DIC due to sepsis and endotoxin shock.
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PMID:Endotoxin-binding synthetic peptides with endotoxin-neutralizing, antibacterial and anticoagulant activities. 783 55

This study aimed to investigate the effects and mechanisms of action of systemic administration of monoclonal antibodies, anti-endotoxin (HA-1A), in an animal model of gut-origin sepsis. In the first experiment, Balb/c mice were transfused with allogeneic blood (C3H/HeJ mice). Five days post-transfusion the animals were gavaged with 1 x 10(9) Escherichia coli and randomized into three groups (n = 22 each) to receive a sham burn (SB group) or a 20 per cent TBSA thermal injury, immediately followed by the systemic administration of monoclonal antibodies (3 mg/kg) (HA-1A group) or aliquots of sterile saline (Control group). The animal survival rate was observed for 10 days postburn. In the second experiment transfusion and burn injury were reproduced but the mice (n = 8/group) were gavaged with 10(9) E.coli labelled with 111indium oxine. Four hours after the burn the mesenteric lymph nodes, liver, lungs and blood were harvested to determine plasma endotoxin levels and the magnitude of translocation of labelled bacteria measured by the residual radioactivity in the organs. Circulating endotoxin levels were determined by limulus assay. The mortality rate of the HA-1A group (9 per cent) was similar to the SB group (0 per cent) and significantly lower than the control group (59 per cent) (P < 0.05). Both plasma endotoxin levels and degree of bacterial translocation in all extraintestinal tissues were significantly lower (by approximately 50 per cent) in the HA-1A group than in the control group (P < 0.05). Systemic administration of HA-1A exerts a beneficial effect by reducing the circulating levels of endotoxin and by increasing the gut barrier function to translocating microorganisms.
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PMID:Experimental gut-derived endotoxaemia and bacteraemia are reduced by systemic administration of monoclonal anti-LPS antibodies. 863 18

The use of operative laparoscopy in gynecologic oncology has paved the way to a more conservative approach in radical treatments of some cancers, particularly cervical cancer. After the vaginal approach which shortens the hospital stay and the morbidity of a radical hysterectomy, a new fertility-preserving radical treatment has been proposed : the Radical Vaginal Trachelectomy (RVT). This technique has been used since 1991 in our institution. Until July 1999, 37 patients with early-stage cervical cancer desiring to retain their fertility were treated by a laparoscopic pelvic lymphadenectomy (LPL) and RVT. The median age was 32 (22-42), and 25 were nulliparous. Twelve were FIGO stage Ia2, 22 Ib1, 2 IIa and one Ia1 (VSI+). Most of the tumors were squamous (23), grade I (21), and the lesion was 2cms or less in 35 patients. Median operating time was 275 minutes ( 200 for the last 10 cases), and blood loss 200cc. Complications were mainly due to the LPL (3 arterial injuries) rather than the RVT (one iatrogenic cystotomy and one parametrial bleeding). The mean follow-up is 42 months. Two patients recurred including one who had a small-cell neuroendocrine tumor. Ten patients had a total of 13 pregnancies with 7 live births. One newborn died of E.coli-septicemia. Two patients had early miscarriages and 2 second trimester abortions (17 and 20 weeks). Two patients are still pregnant. LPL-RVT seems to be a good treatment modality for early-stage cervical cancer. It preserves fertility without lowering the chances of survival.
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PMID:[Radical vaginal trachelectomy for invasive cervical cancer]. 1080 72

Tissue factor (TF) plays an important role in the pathogenesis of atherosclerotic, sepsis and disseminated intravascular coagulation (DIC). TF pathway is therefore an attractive therapeutic target in a number of disease states. Here two TF mutants were developed and named MCsTF and MFsTF, in which the amino acids of active sites were mutated. Both of them were expressed in E.coli and used to inhibit TF pathway through competitive FVII/VIIa binding with TF. The results indicated that rMCsTF almost lost all activities of FX activation and procoagulation, and rMFsTF lost 90% activity. The specific catalytic constant ( k ( cat )/ K (m)) of FX activation by the complex formed by FVIIa with rMCsTF or rMFsTF were 2.0% and 3.7%, respectively, compared to that of rsTF. The inhibition effects of the mutants were studied in vitro, and it appeared that the prothrombin time were prolonged in a dose-dependent manner. Therefore, these mutants of TF may become new kind of specific inhibitors of TF pathway, as a promising drug for the treatment of patients with over-expression of TF.
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PMID:[Molecular cloning, expression and characterization of the clones encoding soluble TF mutants]. 1201 50

The present article is a descriptive analysis of clinical and bacteriological profile of neonatal septicemia in a tertiary care hospital in Bangladesh. Eighty six neonates with suspected sepsis were enrolled, out of which 30 were culture positive. Clinical presentation was non-specific. Majority (70%) of the cultures isolated gram negative bacilli, most commonly E.coli and Klebsiella. These isolates were most often sensitive to gentamicin, ciprofloxacin, and third generation cephalosporins. Twelve out of 30 culture positive cases died.
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PMID:Clinical and bacteriological profile of neonatal septicemia in a tertiary level pediatric hospital in Bangladesh. 1246 74

Tissue factor pathway inhibitor (TFPI) is a physiological inhibitor of extrinsic pathway of coagulation and has biological functions of anticoagulation and anti-inflammation. Although TFPI has been proved to be a good therapeutic agent of sepsis, inflammatory shock, and DIC, the clinical application and therapeutic effects of TFPI are impeded because of its short half-life in vivo. In order to prolong the half-life of TFPI, homology modeling and molecule docking were performed on a computer workstation principally in protein structural biology and binding characteristics between TFPI and its receptor LRP (low-density lipoprotein receptor related protein). Two recombinant long half-life human TFPI mutants coined TFPI-Mut1 and TFPI-Mut4 were designed and expressed in E.coli. In comparison with the wild-type TFPI, TFPI-Mut1 and TFPI-Mut4 presented a few of changes in spatial configuration and a decrease in relative Gibbs free energy of docking complex by 17.3% and 21.5%, respectively, as indicated by a computer simulation. After refolding and purification, anticoagulant activities, anti-TF/FVIIa and anti-FXa activities of the mutants were found to be the same as those of wide-type TFPI. The pharmacokinetics research indicated that alpha phase half-life (t1/2 alpha) of TFPI-Mut1 and TFPI-Mut4 were prolonged 1.33-fold and 1.96-fold respectively, beta phase half-life (t1/2 beta) of TFPI-Mut1 and TFPI-Mut4 were prolonged 1.62-fold and 4.22-fold respectively. These results suggested that TFPI-Mut1 and TFPI-Mut4 maintained the bioactivities of wild-type TFPI, prolonged half-life in vivo simultaneously and were expected for better clinical value and therapeutic effect.
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PMID:Molecular design and characterization of recombinant long half-life mutants of human tissue factor pathway inhibitor. 1596 88

Noma Neonatorum is characterized by a gangrenous process involving mucocutaneous junctions of oral, nasal and anal area and occasionally, the eyelids and scrotum. It is seen during the first few weeks of neonatal life in premature and low birth weight babies. Noma Neonatorum is commonly described with pseudomonas aeruginosa septicemia. A case of Noma Neonatorum associated with E.coli sepsis is described for the first time.
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PMID:Noma neonatorum. 1674 34


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