Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
 4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a phase I clinical investigation of 30-minute and four-hour intravenous (IV) infusions of recombinant tumor necrosis factor (rTNF)-alpha. Thirty-nine patients with disseminated cancer received escalating doses of rTNF-alpha for five consecutive days every 2 weeks for a total duration of 8 weeks. Dose escalations followed a modified Fibonacci scale with a minimum of four patients entered at each dose level: 5, 10, 25, 50, 75, 100, 150, 200, and 250 micrograms/m2/d. Toxicities consisted mainly of constitutional symptoms including fever, chills, headache, and fatigue, increasing in severity with dose escalation. No significant differences in dose-limiting toxicities were seen between the two rates of IV infusion. The maximum tolerated dose (MTD) was 200 micrograms/m2 with dose limiting toxicity being constitutional symptoms and hypotension. Hematologic changes included median decrease in both granulocyte and platelet counts of 38% and 41%, respectively (range, 16% to 85%), although clinically significant granulocytopenia and thrombocytopenia were not observed. Hematological parameters returned to baseline within 72 hours after rTNF-alpha was stopped. rTNF-alpha induced changes in lipid metabolism were manifested by median fasting triglyceride elevations above baseline (median, 103 micrograms/dL) of 157% (range, 16% to 389%) after five days of therapy with doses greater than 75 micrograms/m2, associated with a median increase in very-low-density lipoprotein (VLDL) of 80%. Serum rTNF peak levels exceeding 10 ng/mL were observed 30 minutes following rTNF-alpha infusions at MTD dose. Twelve of 34 patients had no change in their evaluable disease for a median duration of 18 weeks (range, 8 to 30 weeks), and 22 patients showed progressive disease. This study forms the framework for phase II trials of IV administered rTNF-alpha.
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PMID:A phase I trial of intravenously-administered recombinant tumor necrosis factor-alpha in cancer patients. 341 44

Recombinant human tumor necrosis factor (rH-TNF) is a cytokine with direct antitumor properties. In a phase I trial we continuously infused rH-TNF for 24 hours. We gave a total of 115 courses of therapy to 50 patients. Doses ranged from 4.5 to 645 micrograms of rH-TNF/m2. Systemic toxicity, including fever, chills, fatigue, and hypotension, increased with the dose of rH-TNF administered. Doses greater than 454 micrograms/m2 frequently caused severe lethargy and fatigue, which precluded hospital discharge of the patient at the completion of therapy. The dose-limiting toxicity was hypotension, and five patients treated at the two highest dose levels required dopamine treatment. Other organ-specific toxicity was modest and spontaneously resolved after 48 hours. The 24-hour infusions of rH-TNF were associated with significant decreases in serum cholesterol and high-density lipoprotein levels. Pharmacokinetic studies using an enzyme-linked immunosorbent assay demonstrated peak plasma rH-TNF levels of 90-900 pg/mL. Despite continuous infusion of rH-TNF, no steady-state level was achieved. The recommended phase II dose for rH-TNF as a 24-hour continuous infusion is 545 micrograms/m2.
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PMID:Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study. 341 18

Current therapy for condylomata acuminata (genital warts) is not consistently effective. Therefore, we conducted a randomized, double-blind trial to compare interferon alpha-2b with placebo in the treatment of this disorder. Our rationale was that interferon has both antiproliferative and antiviral properties. The placebo or interferon (1 X 10(6) IU) was injected directly into one to three warts three times weekly for three weeks. The injections were well tolerated by both groups of patients. The side effects of fever, chills, myalgia, headache, fatigue, and leukopenia occurred more commonly in the interferon group than in the placebo group, but such effects rarely disrupted daily routines. Only 13 of 296 patients (4 percent) discontinued therapy because of side effects (11 in the interferon group and 2 in the placebo group). Twenty-six other patients were excluded from analysis because of a loss to follow-up or other deviations from protocol, thus leaving 257 patients in the final evaluation. At one week after the completion of therapy, interferon had produced a large and significantly greater reduction in mean wart area (a 62.4 percent decrease), as compared with placebo (a 1.2 percent increase in mean area) (P less than 0.001). At the conclusion of the study (13 weeks after the completion of therapy), the mean wart area was still decreased 39.9 percent below the initial size in the interferon group, whereas it had increased by 46 percent over base-line measurements in the placebo group (P less than 0.001). At the same time, all treated warts had completely cleared in 36 percent of the interferon recipients and in 17 percent of the placebo recipients (P less than 0.001), whereas treated warts progressed in 13 percent of the interferon recipients and in 50 percent of the placebo recipients (P less than 0.001). We conclude that injection of interferon alpha-2b directly into genital warts appears to be an effective and fairly well-tolerated form of therapy.
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PMID:Interferon therapy for condylomata acuminata. 353 60

Patients with nodular lymphoma initially respond to a number of therapies but relapse is common and inexorable with time, and despite further therapy, most patients will ultimately die of their lymphoma. The recent demonstration of their sensitivity to alpha-interferon is promising. The importance of this human antitumor effect is that it is presumably based on mechanisms different from conventional agents. Phase I trials of various doses and schedules of recombinant alpha-interferon have shown that effective serum levels can be obtained by intramuscular (IM), intravenous (IV), or subcutaneous (SC) routes. Virtually all patients experienced some degree of acute toxicity manifested by fever, chills, myalgia, and headache. Tolerance usually developed to acute adverse effects within the first few weeks of therapy, regardless of dose or schedule. Fatigue and anorexia were the most important adverse reactions, occurring during the first two weeks of treatment and generally persisting for the duration of therapy. Occasional adverse effects relating to the central nervous and cardiovascular systems have been reported. Primary laboratory abnormalities observed during treatment include decreases in hematologic parameters and elevations of liver function tests. The clinical efficacy of alpha-interferon, both natural and recombinant, has been demonstrated in both untreated and heavily pretreated patients with nodular lymphoma. The response rate has approached 50% in recent studies; however, less than half were complete responders. Future directions include combination of interferon with cytotoxic agents or other biological response modifiers and use as adjuvant therapy.
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PMID:Alpha-interferon in the treatment of nodular lymphomas. 354 Dec 18

In late April 1984, an outbreak of Pontiac fever was investigated in an office building in lower Manhattan (New York City). The outbreak was characterized by a high attack rate (78 per cent overall); the predominant symptoms were myalgias, chills, fatigue, fever, and headache. There was a clustering of cases in an office that was air cooled by a dedicated cooling tower separate from the remainder of the building. A high concentration of live L. Pneumophila cells in the cooling tower was quantified. Airborne spread via settle plates placed along the air intake system and within the office was demonstrated. Legionella pneumophila serogroup 1 antigen was found in the urine of two cases, and identical monoclonal antibody reactivity patterns of isolates from all sources was observed. Difficulty was experienced in eliminating the organism from the tower.
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PMID:Pontiac fever outbreak associated with a cooling tower. 356 48

Two mixing methods, hand and vacuum mixing, were compared using high viscosity, high molecular, antibiotic containing polymethylmethacrylate kept at two different temperatures, 4 degrees C and 21 degrees C, prior to mixing. The mechanical properties, i.e., fracture strength, maximum deflection, modulus of elasticity and hardness, were improved by vacuum mixing when compared with hand mixing at both temperatures. The fatigue life was 10 times longer after vacuum mixing. Chilling prior to mixing made the mixing easier and improved the handling characteristics. Vacuum mixing delayed the setting time by 1 minute, but also decreased the peak temperature. Radiographic analysis showed that vacuum mixing mainly reduced the microporosity, but also the macroporosity. The mechanical properties deteriorated slightly after 2 months in Ringer's solution, but the differences between the mixing procedures remained unchanged.
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PMID:Bone cement improved by vacuum mixing and chilling. 357 37

A total of 21 patients with advanced metastatic malignant melanoma were treated in this efficacy study of recombinant leukocyte A interferon (interferon alpha-2a). Patients received 18 X 10(6) units interferon alpha-2a by i.m. injection daily for the first 10 weeks and then three times weekly for a further 4 months. The symptoms of toxicity observed in this study resembled those previously reported for alpha interferons and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, dose-dependent reversible leukopenia, and hepatic transaminase elevations. Of the 21 patients, 12 had evidence of tumor progression, 6 had stable disease for at least 2 months, and complete remission was seen in 3 patients with stage III melanoma. We conclude that interferon alpha-2a appears to have some antiproliferative effect in metastatic malignant melanoma. While its use in stage IV patients with big tumor masses is doubtful, there seems to be therapeutic benefit in earlier stages.
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PMID:Phase II trial of recombinant leukocyte A interferon in advanced malignant melanoma. 358 16

Twenty-six patients with recurrent respiratory papillomatosis have received interferon administered according to one or more of five experimental protocols currently ongoing or completed at the University of Iowa. Short-term side effects following interferon administration were common and included fever, headache, chills, fatigue, myalgias, and nausea. Two patients experienced neurotoxicity manifested as somnolence, confusion, or petit mal type or grand mal type seizures. Preliminary data show evidence for some growth retardation in patients receiving long-term interferon therapy. Laboratory evidence of toxicity in the form of decreased WBC, RBC, and platelet counts occurred in five patients, and increased liver enzymes occurred in 16 patients. Neither cardiovascular nor renal toxicity was noted.
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PMID:Side effects and toxicity of interferon in the treatment of recurrent respiratory papillomatosis. 367 59

Three heroin addicts had Candida folliculitis of the scalp, beard, and pubis associated with fever, chills, headache, and fatigue. In each case, pseudohyphae were found within a hair and yeasts around it and Candida was recovered from urine. These facts support a systemic dissemination. Since serious ocular and osteoarticular lesions have been described with this type of skin lesion, prompt diagnosis may be important to initiate treatment and prevent sequelae.
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PMID:Candida folliculitis in heroin addicts. 369 50

Bilateral pulmonary infiltrates developed in a 77-year-old woman. These were associated with chills, fatigue, a high spiking temperature, leukocytosis, and eosinophilia. Clinical symptoms abated after 24 hours, and radiologic abnormalities cleared several days after discontinuing Nalfon, plus administering prednisone. The most likely cause of these pulmonary infiltrates was a hypersensitivity or idiosyncratic reaction to Nalfon.
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PMID:Pulmonary hypersensitivity to nalfon. 375 22


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