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)

We describe a 7-years boy by with a meningococcal sepsis due to Neisseria Meningitidis, with very serious evolution of cutaneous necrosis, initial D.I.C. and heart failure. The clinical picture do not improve with antibiotic therapy (CAF-penicillin), but the association ceftriaxone + tobramycin results in rapid improvement. The cutaneous necrosis, especially evident on gluteus, arms and legs, were treated locally with AgNO3 and penicillin-solution. After 4 weeks of treatment, also this cutaneous involvement improved and now the boy is healthy, without residual signs neither systemic nor cutaneous.
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PMID:[A case of meningococcal sepsis]. 210 79

Fifty-six evaluable patients with advanced ovarian carcinoma (FIGO III or IV), without prior cytotoxic chemotherapy, were studied to assess the activity of single-agent moderate-dose cyclophosphamide, 40 mg/kg to a maximum dose of 3000 mg, given intravenously as a bolus injection every 3 weeks. All patients were treated as outpatients. Moderate-dose cyclophosphamide resulted in 36 (64%) objective responses (19 CR, 17 PR). Nausea and severe vomiting occurred in all patients, but no patient needed hospitalization for this complication. Other side-effects observed were alopecia (100%), leukocytes less than or equal to 2500/microliters (18%), chemical cystitis (11%) and sepsis (4%). The median duration of response was 11 months, and the estimated median survival by the life-table method for responders was 16 months and for non-responders 4 months (P less than 0.001). Clinical trials previously performed by our group comparing cyclophosphamide alone, either vs cis-platinum, adriamycin and hexamethylmelamine or vs Hexa-CAF, showed a better remission rate with the use of moderate-dose cyclophosphamide alone. Therefore we suggest further investigation of this agent in a moderate dose in disseminated ovarian carcinoma.
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PMID:Moderate-dose cyclophosphamide for disseminated ovarian carcinoma: a phase II study. 668 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

CAP18 (cationic antimicrobial protein, 18kDa) is a 142 amino acid protein originally isolated from rabbit granulocytes using agglutination of LPS-coated erythrocytes as an assay. CAP-18 is composed of an N-terminal domain of unknown function (CAP181-105) and a C-terminal LPS-binding domain (CAP18106-142). Synthetic CAP18106-142 and CAP18106-137, a 32-amino acid peptide resulting from the truncation of 5 amino acids from the C-terminus of CAP18106-142, inhibited LPS-induced tissue factor generation, nitric oxide production and TNF release by macrophages. Mice treated with CAP18106-142 or CAP18106-137 were significantly protected from LPS lethality. Although CAP18106-142 and CAP18106-137 were highly active, other fragments of CAP18106-142, including CAP18110-142 with a truncated N-terminus, did not exhibit LPS-binding and LPS-neutralizing activities. Both peptides had broad anti-microbial activity against both Gram-negative bacteria such as Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa (IC50; 40-100 nM) and Gram-positive bacteria such as Staphylococcus aureus(Methicillin sensitive and resistant strains) and Streptococcus pneumoniae (IC50; 100-200nM). We cloned a CAP18 family protein from human granulocytes. The cloned cDNA encoded 140 amino acid residues. Human CAP18 (CAP181-140) was highly homologous to that of rabbit. A 32- amino-acid C-terminal fragment (CAP18104-135) was shown to bind LPS, inhibit LPS-induced tissue factor generation by murine macrophages, and protect mice from LPS lethality. This peptide exhibited antimicrobial activity against both Gram-negative and Gram-positive bacteria. We hypothesize that CAP18 and the derived peptides bind to LPS and alter the capacity of LPS to initiate disseminated intravascular coagulation. In this regard, CAP may act as host defense protein against infectious diseases, and have therapeutic potential for sepsis and endotoxin shock.
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PMID:Structure and functions of endotoxin-binding peptides derived from CAP18. 852 37

One hundred and six patients with endometrial cancer were treated at Tsukuba University Hospital between 1983 and 1992. Sixteen patients who underwent complete resection were at high risk for recurrence and were given adjuvant platinum-based, multiagent chemotherapy instead of adjuvant radiotherapy. Eligibility criteria included outer-third myometrial invasion (group 1; n = 5), pelvic lymph node metastasis (group 2; n = 3) or both myometrial invasion and lymph node metastasis (group 3; n = 8). Of these three groups at high risk for recurrence, each patient in groups 1 and 2 developed recurrence and died. In group 3 two patients developed recurrence and one patient has died. There was one treatment death due to neutropenic sepsis in group 3. The recurrence sites in all four patients were local and no distant recurrence was noted. In other words, of 15 patients (excluding one treatment death) at high risk for recurrence, three of 12 patients (25%) with deep myometrial invasion and three of 10 patients (30%) with positive pelvic lymph nodes developed recurrence and died. The other 12 patients (include one patient with recurrence; 100 months) have survived for a long interval (range, 45-131 months). The survival rates for stage I, II, III, and IV are 92.6, 89.5, 60.0%, respectively. Patients with stage I in this study had a better survival than those with stage I in the 1984 annual report of the Japan Society of Obstetrics and Gynecology (p < 0.05). The findings of this prospective clinical trial supported those of the randomized trial comparing adjuvant CAP with radiation therapy.
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PMID:[Adjuvant chemotherapy with cyclophosphamide, adriamycin, and CDDP (CAP) for high risk endometrial cancer after complete surgery]. 857 21

Severe CAP is a life-threatening condition defined by the presence of respiratory failure or symptoms of severe sepsis or septic shock. It accounts for approximately 10% of hospitalized patients with CAP. The majority of patients with severe pneumonia have underlying comorbid illnesses, with COPD, alcoholism, chronic heart disease, and diabetes mellitus being the most frequent. S. pneumoniae, Legionella spp, GNEB (especially K. pneumoniae), H. influenzae, S. aureus/spp, Mycoplasma pneumoniae, respiratory viruses (especially influenza viruses), and P. aeruginosa represent the most important causative organisms of severe CAP. Rapid initiation of appropriate antimicrobial treatment is crucial for a favorable outcome. Initial antimicrobial treatment should be based on an epidemiological (empiric) approach. Microbial investigation may be helpful in the individual case but is probably more useful to define local antimicrobial policies based on local epidemiologic and susceptibility patterns. Mortality rates range from 21% to 54%. The most important prognostic factors include general health state of the patient, appropriateness of initial antimicrobial treatment, and the existence of bacteremia, as well as factors reflecting severe respiratory failure, severe sepsis, septic hypotension or shock, and the extent of infiltrates in chest radiograph. Initial antimicrobial treatment should consist of a second (or third) generation cephalosporin and erythromycin. Modifications of this basic regimen should be considered in the presence of distinct comorbid conditions and risk factors for distinct pathogens. Promising new approaches of nonantimicrobial treatment, including noninvasive ventilation, treatment of hypoxemia, and immunomodulation, are under investigation.
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PMID:Severe community-acquired pneumonia. 1051 5

Many antimicrobial peptides and proteins were discovered recently in various animals. Cecropins are insect-derived antimicrobial peptides which contain 35-39 amino acid residues. Magainins are amphibian-derived antimicrobial peptides with 21-27 amino acid residues. In mammals, defensins, 29-35 amino acid peptides, were identified in the granules of neutrophils and various epithelial cells. In addition, the granules of neutrophils in the mammal have been shown to have several antimicrobial proteins. Among them, bactericidal/permeability increasing protein (BPI) and cationic antimicrobial peptide-18 (CAP 18) have been found to have potent bactericidal activity against gram-negative bacteria and strong lipopolysaccharide-neutralizing function. The recombinant BPIs (recombinant BPI, 23-kDa N-terminal fragment of BPI, and lipopolysaccharide-binding protein-BPI fusion protein) and synthetic peptides derived from C-terminal of CAP 18 are now under investigation for the application to the therapy of sepsis or septic shock.
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PMID:[Antimicrobial peptides/proteins--application to the therapy of sepsis]. 1058 50

It seems that with climatic and geoecologic changes, Hantaviruses have re-emerged as human pathogens related to increases in interaction between humans and rodent reservoirs. Infection with SNV in North America and the Andes virus in South America can produce infection manifest initially as a flu-like illness. In the setting of a history of possible exposure to rodents or their excreta, clinical symptoms and laboratory clues such as thrombocytopenia should raise the suspicion of HPS. Clinical deterioration can be rapid, so patients should be hospitalized and transported to tertiary care centers where mechanical ventilation is available if necessary. Presumptive treatment for other forms of sepsis should be considered before confirmation of diagnosis. Survival seems to be determined in part by viral and host factors. Canadian and South American data suggest that there may be species variations influencing clinical manifestations and course of disease. Because the pathogenesis seems to be based on immunologic injury, future treatments will likely focus on interventions other than antiviral medications. Prevention strategies should be emphasized, particularly when recognized climatic conditions favor rodent abundance. Physicians should remain alert to the possibility of such a diagnosis when evaluating a patient with CAP and should request appropriate serology while supporting the patient in a closely monitored setting. The declining mortality rates seen over the past decade may be a consequence of improved medical management or better recognition of cases, including those less severe than originally described.
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PMID:Community-acquired pneumonia: new facets of an old disease--Hantavirus pulmonary syndrome. 1576 21

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presented to an emergency department (ED), and it is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. For diagnosing CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in elderly population, and in patients with renal dysfunction. They might have also a prognostic value. Studies demonstrated that the use of BNP or NT-proBNP in dyspneic patients early in the ED reduced the time to discharge, total treatment cost. BNP and NT-proBNP should be available in every ED 24 hours a day, because literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients.Etiologic diagnosis of febrile patients who present to an ED is complex and sometimes difficult. However, new evidence showed that there are interventions (including early appropriate antibiotics), which could reduce mortality rate in patients with sepsis. For diagnosing sepsis, procalcitonin (PCT) is more accurate than C-reactive protein. Thus, because of its excellent specificity and positive predictive value, an elevated PCT concentration (higher than 0.5 ng/mL) indicates ongoing and potentially severe systemic infection, which needs early antibiotics (e.g. meningitis). In lower respiratory tract infections, CAP or COPD exacerbation, PCT guidance reduced total antibiotic exposure and/or antibiotic treatment duration.
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PMID:Useulness of B Natriuretic Peptides and Procalcitonin in Emergency Medicine. 1957 5

Appropriate antibiotic management and aggressive supportive therapy is not enough to improve survival in severe community-acquired pneumonia (sCAP), a systemic syndrome involving infectious organisms, inflammation, and coagulation systems. A sepsis severity staging system focused on predisposition, insult, deleterious response, and organ failure (PIRO) provides a useful basis for risk stratification and therapy. A new paradigm of management is suggested based on early identification of patients at risk, aggressive management, modulation of host response, and need for adjunctive therapy. The CAP-PIRO score is a new, simple tool stratifying patients in four categories and may be useful for early identification of patients who may benefit from adjunctive therapy.
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PMID:Severe community-acquired pneumonia and PIRO: a new paradigm of management. 1969 77


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