orabase and Fever

Topics: Adolescent; Adult; Aged; Carboxymethylcellulose Sodium; Child; Child, Preschool; Clinical Trials as Topic; Drug Evaluation; Female; Fever; Humans; Hypotension; Infant; Interferons; Leukemia; Male; Methylcellulose; Middle Aged; Neoplasms; Peptides; Poly I-C; Polylysine

Twenty-five patients with metastatic carcinoma were entered into a Phase I clinical trial using poly(I,C)-LC at either 1 mg/m2 or 4 mg/m2 intravenous, twice weekly, for 4 weeks. None of the 15 patients entered at the 1 mg/m2 dose had an objective response; three had progressive disease. Similarly, no objective responses were observed among the 10 patients treated at the 4 mg/m2 dose of poly(I,C)-LC; one patient was removed from the study due to progressive disease. Toxicities observed at the 1 mg/m2 dose were mild hypotension, fever, nausea, vomiting, fatigue, and headache. The first patient treated at the 4 mg/m2 dose was taken off of the study for severe hypotension. In the subsequent nine patients treated at this dose, a pretreatment with one dose at 1 mg/m2 was given, and no further problems with hypotension were encountered. The other toxicities at 4 mg/m2 were similar to those seen at 1 mg/m2.

Topics: Carboxymethylcellulose Sodium; Drug Evaluation; Fever; Humans; Hypotension; Interferons; Kinetics; Methylcellulose; Nausea; Neoplasms; Poly I-C; Polylysine

Sixteen patients with metastatic malignant melanoma were treated with poly(I,C)-LC 5 mg/m2 twice weekly by intravenous injection. No antitumor responses occurred. Fever (frequently greater than 40 degrees C) and fatigue were dose limiting toxicities. One patient developed a fever of 42.2 degrees C when poly(I,C)-LC was given on 2 consecutive days. Interferon was consistently detected in the serum 8 h after a single injection of poly(I,C)-LC (median titer 199 U/ml). No enhancement of interferon induction was detected on the second day when poly(I,C)-LC was given on 2 consecutive days.

Topics: Adult; Aged; Antineoplastic Agents; Carboxymethylcellulose Sodium; Drug Evaluation; Fatigue; Female; Fever; Humans; Interferons; Male; Melanoma; Methylcellulose; Middle Aged; Poly I-C; Polylysine

The ability of polyriboinosionic acid [poly(rI)].polyribocytidylic acid [poly(rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) complexed with poly L-lysine and carboxymethylcellulose [poly(ICLc)] to induce interferon and the comparative toxicity of each in cats were evaluated. Each induced high levels of circulating interferon, although poly(ICLC) injected intravenously at 1 to 4 mg/kg induced up to 10 times more interferon than the other compounds. Each compound was pyrogenic and caused a transient decrease in leukocyte numbers. Poly(rI).poly(rC) and the mismatched analog caused severe diarrhea and nausea at the highest drug concentrations (1 to 4 mg/kg), but poly (ICLC) did not. Each compound also caused depression and lethargy and impaired coordination.

Topics: Animals; Carboxymethylcellulose Sodium; Cats; Dose-Response Relationship, Drug; Female; Fever; Interferon Inducers; Interferons; Leukocyte Count; Male; Methylcellulose; Peptides; Poly C; Poly I; Poly I-C; Polylysine; Polyribonucleotides; Time Factors

In an earlier study the physiological effects encountered in humans of a modified complex of polyriboinosinic acid-polyribocytidylic acid [poly(I)-poly(C)] with carboxymethylcellulose and poly-L-lysine [poly(ICLC) (9S)], namely, the induction of high titers of serum interferon along with fever and hypotension, were reproduced in rabbits. In the present studies, also in rabbits, we evaluated effects of complexes with homopolymer polyribonucleotide sedimentation coefficients decreasing from 9S to 6S and 4S. Modified complexes of carboxymethylcellulose and poly-L-lysine with decreasing molecular weights were also tested. In several studies diphenhydramine and indomethacin were administered concomitantly. These experiments showed that at a daily intravenous dose of 0.2 mg/kg the various preparations of poly(I)-poly(C) (9S) and poly(I)-poly(C) (6S) induced falls in blood pressure, but stabilized complexes of poly(I)-poly(C) (4S) did not. Alterations in the molecular weights of carboxymethylcellulose and poly-L-lysine n the modified complex and the concomitant administration of diphenhydramine did not influence the occurrence or severity of untoward reactions. In rabbits, poly(ICLC) (4S) along with indomethacin induced high titers of serum interferon without fever or hypotension.

Topics: Animals; Blood Chemical Analysis; Blood Pressure; Carboxymethylcellulose Sodium; Fever; Interferons; Leukocyte Count; Male; Poly I-C; Polylysine; Rabbits

The purposes of this study were to determine whether the febrile and hypotensive reactions to the administration of polyriboinosinic-polyribocytidylic acid [poly (I)-poly (C)] complexed with poly-L-lysine and carboxymethylcellulose (poly ICLC) (9S) encountered in humans could be duplicated in rabbits, and when such duplication was demonstrated, to ascertain whether these untoward reactions could be avoided by (i) administration of hydrocortisone (HC), (ii) alteration of the route of delivery, or (iii) administration of poly ICLC (4S) an interferon inducer of lower molecular weight. Responses to intravenous poly ICLC (9S) in rabbits reproduced adverse reactions in humans, namely fever and hypotension, and were accompanied by high titers of serum interferon. Continuing investigations showed that (i) intravenous pretreatment of rabbits with HC ameliorated hypotensive responses but markedly diminished interferon induction. When HC was given after poly ICLC (9S), both interferon and hypotension induction were likewise depressed. (ii) Intramuscular or subcutaneous poly ICLC (9S) produced neither high titers of serum interferon nor toxic effects. (iii) Poly ICLC (4S) induced high titers of serum interferon and fever, but no hypotension. Poly ICLC (4S) warrants further study.

Topics: Animals; Blood Pressure; Body Temperature; Carboxymethylcellulose Sodium; Fever; Hydrocortisone; Hypotension; Interferons; Male; Poly I-C; Polylysine; Rabbits; Time Factors

Fourteen patients with severe viral illnesses were given intravenous infusions of a modified interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly)I:C.LC)], during a phase 1 clinical trial. The first eight patients received 0.15 to 0.30 mg of poly(I:C.LC) per kg of body weight daily for 5 consecutive days, and another received two courses separated by 1 week. A second group of five patients was given single intravenous infusions of 0.10 to 0.15 mg of poly(I:C.LC) per kg. Interferon was detectable in the serum 8 to 16 h after injection. Titers ranged from 15 to 800 U/ml and varied directly with the dose of poly(I:C.LC). Interferonemias persisted for 12 to 48 h. In patients receiving 5-day courses of poly(I:C.LC), lower levels of serum interferon (0 to 160 U/ml) occurred on days 2 through 5, characteristic of a hyporesponsive state. An exception was a 69-year-old patient with disseminated varicella zoster, multiple myeloma, and renal insufficiency whose serum contained 3,150 U of interferon per ml on day 3 of 0.3 mg of poly(I:C.LC) per kg. Fever (39 to 40.5 degrees C, rectally; 13 of the 14 patients) peaked 3 to 8 h after completion of infusions. Other toxic effects included lymphopenia (10 of the 14 patients), hypotensive episodes (7 of the 14 patients), and minor elevations of serum glutamicoxalacetic transaminase and lactic dehydrogenase.

Topics: Adolescent; Adult; Aged; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Fever; Humans; Hypotension; Interferons; Liver; Lymphopenia; Male; Poly I-C; Polylysine; Virus Diseases

Polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose [poly(ICLC)] enhances the antibody response in rhesus monkeys immunized with swine influenza virus subunit vaccine. Monkeys given the vaccine-adjuvant combination had earlier and significantly (P less than .05) higher titers by 14 days compared to those that received vaccine alone. The potentiation of the antibody response of young monkeys given a split-virus vaccine in combination with poly(ICLC) suggests that this vaccine-adjuvant combination may similarly provide a potentially useful alternative approach to the immunization of pediatric and young adult age groups against swine influenza.

Topics: Adjuvants, Immunologic; Age Factors; Animals; Antibodies, Viral; Carboxymethylcellulose Sodium; Female; Fever; Haplorhini; Influenza A virus; Influenza Vaccines; Macaca mulatta; Male; Peptides; Poly I-C