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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The physiological immunodeficiency of preterm and term newborns is the major cause of their increased susceptibility to infections. Although nonspecific and specific host defence mechanisms are morphologically intact, there are functional and quantitative defects. Supportive immunotherapy is required to equalize these immunological defects. This article reviews topical possibilities for immunotherapy of neonatal sepsis (exchange transfusion, transfusion of fresh blood or fresh plasma, granulocyte transfusion, use of immunoglobulins, fibronectin, interferon and colony-stimulating factor).
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PMID:[Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 2: Immunotherapy]. 223 77

Recombinant interferon alfa-2a (rIFN alpha-2a) synergistically augments the cytotoxic effects of the antimetabolite fluorouracil (5-FU) against two human colon cancer cell lines. A pilot clinical trial was initiated to determine whether this same combination of agents would show clinical utility greater than that expected with 5-FU alone in patients with advanced colorectal carcinoma. 5-FU was administered at 750 mg/m2/d for 5 days as a continuous intravenous infusion followed by weekly bolus therapy. rIFN alpha-2a was administered at 9 million units subcutaneously three times per week starting on day 1. Doses of 5-FU were modified for mucosal toxicities and myelo-suppression, and doses of rIFN alpha-2a were modified for fatigue and neurologic toxicities. Thirty-two previously untreated patients with advanced colorectal carcinoma were entered into a clinical trial. With the exception of one patient with a destructive lesion of the sacrum, all patients had metastases to visceral organs, abdominal wall, or pelvis. Twenty patients (63%) achieved a partial response, seven remained stable, and five had progressive disease. Mucosal toxicities limited delivery of full projected dose. Two patients died following episodes of watery diarrhea progressing to sepsis. A third died suddenly, secondary to an interstitial pneumonitis. The remainder of the toxicities were managed with dose reductions. At the median follow-up of 8 months, 23 of 32 patients remain alive. Nine are alive at 16 to 30+ months. The early results of this single-institution study are promising, but will require confirmation in a multi-institutional setting currently being conducted by the Eastern Cooperative Oncology Group.
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PMID:Clinical update on the role of fluorouracil and recombinant interferon alfa-2a in the treatment of colorectal carcinoma. 240 91

2',3'-dideoxycytidine (ddC) inhibits replication of the immunodeficiency inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations ranging from 1-10 micrograms/ml. Additive antiviral effect is achieved when ddC is combined with either human recombinant alpha interferon (IFN alpha) or tumor necrosis factor (TNF) plus IFN alpha. Initial in vivo pharmacokinetic studies in cats, utilizing bolus intravenous administration of ddC (20 mg/kg), resulted in peak plasma concentrations of 15 micrograms/ml 1 min after administration and a half-life of approximately 1 h. These values could not be augmented with high levels of the deaminase blocker tetrahydrouridine administered prior to or concurrently with ddC. In vivo trials utilizing multiple, daily intravenous injections of ddC could not prevent the development of persistent viremia in cats infected with FeLV-FAIDS. To enhance ddC pharmacokinetics and antiviral activity, controlled release capsular implants were developed by blending ddC with a copolymer consisting of DL-lactide glycolide and hydroxypropyl cellulose, which was melt-spun into fibers and encapsulated in a sheath of polyethylene glycol for subcutaneous implantation. Pharmacokinetic studies, conducted in cats receiving an average dose of 600 mg of ddC, indicated an average peak plasma concentration of 17 micrograms/ml achieved at 6 h post implantation with 3.5 micrograms/ml noted at 48 h; and an extension of plasma half-life from 1.5 (bolus subcutaneous injection) to 20 h. sustained plasma concentrations of 1.5 to 10 micrograms/ml, equivalent to ddC levels previously shown to have anti-FeLV activity in vitro, were maintained throughout a 72 h period. Implantation devices could be replenished every 48 h and elevated plasma levels were sustained for four weeks without signs of clinical toxicity, sepsis or significant alterations in the hemogram. Initial clinical trials employing controlled release capsular ddC implants in vivo indicate significant retardation of FeLV-FAIDS replication throughout a four week treatment period.
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PMID:Treatment of FeLV-induced immunodeficiency syndrome (FeLV-FAIDS) with controlled release capsular implantation of 2',3'-dideoxycytidine. 254 37

Based on in vitro studies that have demonstrated synergy between recombinant alfa-2a-interferon (rIFN alpha-2a) and the fluoropyrimidine, fluorouracil (5FU), against two human colon cancer cell lines, a pilot clinical trial was initiated to determine the effects of the combination of 5FU and rIFN alpha-2a in patients with advanced, unresectable colorectal carcinoma. A total of 30 patients were enrolled; all were evaluable. 5FU was administered as a loading course, 750 mg/m2 daily for 5 days by continuous infusion followed by weekly bolus therapy, rIFN alpha-2a, 9 MU, was administered subcutaneously three times per week. Of 17 previously untreated patients evaluable for response, 13 achieved a response. Three patients had disease progression. No previously treated patients had a major response. There was one death clearly related to therapy, an event preceded by watery diarrhea and neutropenic sepsis. Other toxicities were reversible and responded to dose reduction. With a median follow-up of 16+ months, median survival has not been reached among the previously untreated patient cohort. We conclude that the combination of 5FU and rIFN alpha-2a is an active regimen against disseminated colorectal cancer in previously untreated patients.
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PMID:Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma. 258 16

Recombinant interferon (rIFN) modulates the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), in in vitro experimental tumor cell systems. In three clinical trials employing rIFN and 5FU in patients with advanced colorectal carcinoma conducted at the Albert Einstein College of Medicine, more than half the patients achieved an objective response. Of interest, the clinical spectrum of toxicities observed with this combination is different from those seen with either rIFN or 5FU alone. This novel constellation of toxicities includes a clinical syndrome characterized by watery diarrhea followed by life-threatening sepsis. Thus, careful observation and characterization of these toxicities are required. Patient education, with the goal of making patients recognize serious side effects, is important in the management of these patients.
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PMID:Clinical toxicities of the combination of 5-fluorouracil and recombinant interferon alfa-2a: an unusual toxicity profile. 259 51

A survey is given of the occurrence, the biochemical qualities and the various functions of macrophages. By binding of gamma-interferon and of waste products of bacteria they are activated and increasedly give off interleukin 1 and other compounds, which play a part in the evocation of the immune reaction and the inflammatory processes. The interleukin 1 causes the evocation of fever, an increase of the secretion of corticoliberin and of ACTH, an increase of the formation of the proteins which are increasedly effective in the acute phase of the inflammation as well as an activation of B- and T-lymphocytes. For the phagocytosis, among others, the fibronectin is of importance, the content of which in the blood plasma is greatly reduced in sepsis and after severe burns. In macrophages an elaboration of numerous antigens takes place which are then transferred into the membrane and under participation of glycoproteins of MCH II cause an activation of T-lymphocytes.
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PMID:[Some recent facts on the function of macrophages and their modification]. 265 17

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

Intranasally administered alpha/beta interferon blocked extension of the coronavirus, mouse hepatitis virus, strain JHM (MHV-JHM), from the nose to the brain of BALB/cByJ mice following intranasal inoculation with the virus. Two hundred units of alpha/beta interferon were administered intranasally to BALB/cByJ mice daily over a five day period. The mice were exposed intranasally to 10(3) median tissue culture infectious doses of MHV-JHM on the third day of interferon treatment. Two days after virus exposure, the proportion of mice with MHV in nasal turbinates was reduced from 10 of 10 in the untreated group to 7 of 10 in the interferon-treated group, and mean titers in virus-containing noses were lower in the interferon-treated group. Five days after virus exposure, the proportion of mice with infectious virus in the brain was significantly lower in the interferon-treated group (1 of 10 mice) than in the untreated group (10 of 10 mice). Systemic infection, as measured by presence and concentration of virus in the spleen, was not affected by intranasal interferon treatment. These results suggest that intranasally administered interferon protects against local extension of MHV-JHM from nose to brain, but not against dissemination of virus to other organs, such as the spleen.
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PMID:Intranasally administered alpha/beta interferon prevents extension of mouse hepatitis virus, strain JHM, into the brains of BALB/cByJ mice. 283 42

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


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