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)

Leikinferon was used in multimodality treatment of sepsis caused by gram-negative microorganisms and staphylococci in 33 neonates and infants. It was injected in a dose of 10,000 IU and was given in courses of 4-6 intramuscular administrations with an interval of 48 hours. The treatment with leikinferon promoted a steady improvement of the clinical status, associated with pronounced activation of the interferon system and neutrophilic phagocytosis. The use of the drug in septic shock did not produce any noticeable affect. Fever was the only side effect induced by drug administration. In some children, the temperature rose by 1-1.5 degrees C. It returned to normal after 10-14 hours.
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PMID:[Leukinferon in the combined therapy of infection in neonates and infants]. 266 67

Because of the possible involvement of cytokines in gram-negative septicemia, we investigated serum levels of tumor necrosis factor alpha, interleukin-1 beta, alpha interferon, and gamma interferon in children with gram-negative sepsis and purpura fulminans. We studied 55 patients (ages, 1 month to 19 years) with a clinical diagnosis of sepsis and purpuric lesions who were in shock or had three or more other biologic risk factors. The mortality rate was correlated with the number of risk factors present on admission to the hospital (P = 0.03). Tumor necrosis factor alpha was elevated in 91 percent of the 35 patients tested, interleukin-1 in 21 percent of the 33 patients tested, and gamma interferon in 19 percent of the 32 tested. Alpha interferon levels were within normal limits in the 32 patients tested. Serum levels of tumor necrosis factor alpha were positively correlated with the number of risk factors (P less than 0.05) and negatively correlated with blood fibrinogen levels (P = 0.01). Tumor necrosis factor alpha, interleukin-1, and gamma interferon were significantly higher in patients who died than in the survivors. Alpha interferon levels were similar in the two groups. Serum concentrations of both interleukin-1 and gamma interferon were correlated with concentrations of tumor necrosis factor alpha. These data provide evidence that serum levels of tumor necrosis factor alpha, interleukin-1, and gamma interferon correlate with the severity of meningococcemia in children. The findings may have implications for new therapeutic approaches.
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PMID:Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. 313 97

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.
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PMID:Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. 359 2

Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.
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PMID:Human lymphoblastoid interferon for hairy cell leukemia: results from the Italian Cooperative Group. 366 57

We have tested the hypothesis that tumor necrosis factor (TNF), by binding to and activating granulocytes, may contribute to the pathogenesis of gram-negative sepsis and the adult respiratory distress syndrome (ARDS). Buffy coat granulocytes incubated with as little as 0.5 ng/mL of recombinant TNF (rTNF) showed a dose-related increase in nitroblue tetrazolium dye reduction, in granulocyte polarization, in superoxide anion release, and in visually apparent aggregation. Purified lipopolysaccharide (1 microgram/mL) caused polymorphonuclear (PMN) aggregation and activation that was neutralized by polymyxin B. The release of superoxide was augmented by preincubation of the PMNs with gamma-interferon. The effect of TNF was neutralized by TNF-specific murine monoclonal antibodies but not by polymyxin B. Scatchard analysis of 125I-rTNF binding to granulocytes revealed about 1,200 receptors per cell with a Kd of 4.9 X 10(-10) mol/L. These results suggest that the release of TNF by mononuclear phagocytes contributes to granulocyte activation and aggregation during inflammation.
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PMID:Recombinant tumor necrosis factor causes activation of human granulocytes. 380 73

Administration of leukocytic interferon to patients with sepsis and purulent resorptive fever resulted in a reliable increase in the indices of the host protective factors with respect to the infections. Addition of interferon to the surgical and antibacterial treatment promoted a decrease in the periods providing the clinical effect to 19.8 days against 43.8 days in the treatment without interferon.
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PMID:[Enhanced activity of the protective factors in patients with suppurative surgical infection using interferon preparations]. 387 58

Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.
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PMID:A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer. 647 Jul 52

The influence of tumor load, surgical trauma, and bacterial sepsis upon the ability of patient's peripheral leukocytes to produce interferon-alpha (IFN-alpha), the detectable serum IFN levels and circulating serum IFN inactivators were studied. Peripheral blood leukocytes of patients with solid tumors had significantly reduced ability to produce IFN-alpha. Complete resectional surgery resulted in restoration of their ability to produce normal IFN-alpha levels. Circulating IFN levels were detectable in 70% of patients with localized disease while only in 20% of patients with metastatic disease. Interferon-alpha activators were detected in 45% of all patients. Both circulating interferon and IFN-alpha inactivators became undetectable upon tumor resection. Surgical trauma is accompanied by a transient but definite decrease in IFN-alpha production capability. Bacterial sepsis during postoperative days, in patients who successfully recovered, was definitely accompanied by increase in IFN-alpha production capability. Our findings suggest that advanced malignant epithelial tumors have an adverse effect upon the patient's ability to produce interferon and are often accompanied by the presence of circulating serum interferon inactivators. These effects can be reversed by surgical resection of the malignant neoplasm.
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PMID:The effect of malignant epithelial tumors, surgical therapy, and bacterial sepsis upon various parameters of interferon system. 672 84

Marked elevation of transforming growth factor-beta 1 (TGF-beta 1) has been demonstrated clinically following injury and in sepsis. While alterations in the monocyte binding site (CD14) for the lipopolysaccharide (LPS)-lipopolysaccharide binding protein (LBP) complex have been noted with exposure to LPS, immune complexes, gamma-interferon, and IL-4, it is not known whether TGF-beta 1 can alter CD14 expression. To study the effect of TGF-beta 1 on monocyte CD14 expression, human leukocytes were isolated from healthy donors with discontinuous gradient centrifugation and incubated at 37 degrees C for 2 and 24 hr with increasing doses of purified human platelet TGF-beta 1. Monocytes were immunofluorescently stained with monoclonal antibodies recognizing CD14 and CD16. The cells were analyzed by flow cytometry. At 2 hr, 50 ng/ml TGF-beta 1 significantly lowered CD14 expression (51%, P = 0.043). At 24 hr, there was no significant difference between cells stimulated by TGF-beta 1 and control cells. To confirm that TGF-beta 1 was active at 24 hr, we examined levels of CD16. CD16 expression was increased by 10 ng/ml of TGF-beta 1. These observations suggest that high physiologic concentrations of TGF-beta 1 cause early monocyte suppression of CD14. Thus, CD14 may be marker for the transition of monocytes to macrophages and TGF-beta 1 may be responsible for the down-regulation of CD14 expression observed in monocytes obtained from septic patients.
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PMID:Transforming growth factor-beta 1 lowers the CD14 content of monocytes. 752 45

We have previously demonstrated that staphylococcal enterotoxins contribute to arthritis and mortality during staphylococcal infection. To further explore the mechanism by which bacterial superantigens contribute to the pathogenesis of Staphylococcus aureus septicemia, T-cell receptor V beta 3 transgenic (TGV beta 3) mice and nontransgenic (non-TG) littermates were inoculated intravenously with S. aureus AB-1, which produces large amounts of staphylococcal enterotoxin A, which specifically reacts with T-cell receptor V beta 3. Within 9 days after inoculation, 85% of the TGV beta mice died, compared with 31% of their non-TG littermates (P < 0.01). The high mortality of TGV beta 3 mice was accompanied by elevated bacterial burdens in the blood, spleen, and kidneys. The in vivo kinetics of cytokine mRNA expression was studied by an in situ hybridization technique. Staphylococcal infection gave rise to increased expression of interleukin 1 beta (IL-1 beta) mRNA and sparsely expressed tumor necrosis factor alpha (TNF-alpha), IL-4, and IL-10 mRNAs in both groups. Gamma interferon mRNA expression increased on day 3 and was maintained at a detectable level in the late phase of infection in TGV beta 3 mice, in contrast to non-TG mice. Impressively, significantly higher expression of TNF-beta mRNA in TGV beta 3 mice was noted throughout the course of infection than in non-TG littermates. These findings suggest that overproduction of TNF-beta and gamma interferon, the Th1 cytokines, may play a crucial role in the pathogenesis of septicemia caused by enterotoxin-secreting staphylococci.
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PMID:Overexpression of the T-cell receptor V beta 3 in transgenic mice increases mortality during infection by enterotoxin A-producing Staphylococcus aureus. 759 Oct 86


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