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)

In vitro studies have documented the synergistic antiviral and antiproliferative activity of recombinant interferon alpha (rIFN alpha) and rIFN gamma. Furthermore, rIFN gamma is a strong immunomodulator with optimal effects at a relative low dose (0.1 mg/m2). On the basis of these observations, we began a phase I/II study with the combination of rIFN gamma at 100 micrograms/m2 (2 x 10(6) IU/m2) and rIFN alpha 2c 6 micrograms/m2 (2 x 10(6) IU/m2), injected twice a week subcutaneously. In cases of stable or progressive disease we increased the dose of rIFN alpha 2c every 2 weeks by 6 micrograms/m2 until the maximum tolerated dose was reached. A total of 32 patients with proven progressive renal-cell carcinoma were included. Of the 31 eligible patients, 21 were male and 10 female, their average age was 57.2 years (range 35-72), 28 had had nephrectomy, their median Karnofsky performance status was 90% (70%-100%), and their tumors were localized predominantly to visceral tissue. In 2, response was complete and in 6 it was partial, for a response rate of 25%. The disease had stabilized in 5 patients and progressed in 16. The median duration of partial response was 14 months (8-16 months); of 2 cases of complete response, 1 persists (23+ months), and the other suffered a relapse after 22 months. The median time to response was 24 weeks (18-24 weeks). The maximum tolerated dose of rIFN alpha was 30 micrograms/m2 (range of 6-36 micrograms/m2). Side-effects included those known to be associated with interferon treatment. One patient developed septicemia during a period with grade 4 leukopenia. Our study permits no conclusion regarding the additional value of rIFN gamma.
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PMID:Phase I/II study of recombinant interferon alpha and gamma in advanced progressive renal-cell carcinoma. 211 17

The in vivo effects of a single prophylactic dose of recombinant bovine interferon (rBoIFN)-alpha I1 in calves with salmonellosis were investigated, using a Salmonella typhimurium infection model. Treatment with rBoIFN-alpha I1 reduced the degree of septicemia compared with that in control groups, and, in one experiment, using disease of reduced severity, body temperature was lower in treated calves than in controls.
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PMID:Prophylactic effects of recombinant bovine interferon-alpha I1 on acute Salmonella typhimurium infection in calves. 220 41

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.
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PMID:Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. 221 80

We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.
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PMID:Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma. 223 Aug 94

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


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