Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients with advanced metastatic adenocarcinomas were treated in a phase-I study with continuous intravenous 24 h infusion of recombinant tumor necrosis factor alpha (TNF-alpha) in order to determine the maximum tolerated dose (MTD) and associated side-effects. Patients received 40-400 micrograms/m2 TNF-alpha once (arm A) or twice (arm B) weekly for a scheduled treatment period of 2 months. The observed systemic side-effects resembled those reported for interferons and included fever, chills, fatigue, headaches, myalgias, thrombocytopenia, prostration, and malaise. Dose-limiting toxicities, resulting in a median MTD of 200 micrograms/m2 for 24 h, were fever, chills, fatigue, myalgias, and thrombocytopenia. Out of 15 patients, 11 showed tumor progression, and 3 sustained in no change for over 2 months of treatment. A minor response was seen in 1 patient with a colorectal carcinoma and liver metastases. To reduce side-effects, patients were treated either with paracetamol or indomethacin. Higher MTDs were observed in patients treated with indomethacin. No detectable plasma TNF-alpha levels or TNF antibodies were measured under therapy (plasma TNF-alpha less than 20 pg/ml). We conclude that TNF-alpha appears to have some antineoplastic activity in patients with adenocarcinomas since 4 patients remained in no change or showed a minor response.
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PMID:Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas. 265 35

A principal side effect of biological response modifiers (BRMs) is a constellation of constitutional symptoms often referred to as a "flu-like syndrome" (FLS). Precisely what this syndrome encompasses is frequently unclear, but its major components appear to be fever, chills, rigors, myalgias, and headache. Other components variously included are anorexia, nausea, upper respiratory symptoms such as nasal congestion and cough, and the ill-defined symptom, malaise. The manner in which the "flu-like" syndrome manifests itself during treatment with interferon (IFN), interleukin-2 (IL-2), tumor necrosis factor (TNF), monoclonal antibodies (MoAbs), and colony stimulating factors (CSFs) will be described with attention to frequency, duration and severity. The common mechanisms underlying the appearance of a flu-like syndrome during biotherapy will be elucidated with emphasis on the role of endogenous pyrogens and prostaglandins and on the physiology of the process. Methods to prevent or alleviate these uncomfortable side effects, including medical interventions such as alterations in schedule/route/dose of BRM administration and premedication with a variety of agents, as well as nursing measures such as patient education will be discussed.
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PMID:Recent advances in the management of biotherapy-related side effects: flu-like syndrome. 268 12

A 32-year-old black man from rural southeastern Texas had headache, fever, chills, bronchopneumonia, and an atypical rash, complicated by hypotension, lethargy, confusion, liver dysfunction, thrombocytopenia, and acute renal failure. The diagnosis of Rocky Mountain spotted fever (RMSF) was not suspected until eight days after the onset of symptoms. He was subsequently treated with chloramphenicol, followed by hemodialysis and aggressive supportive therapy. He recovered uneventfully with complete return of renal function. This case emphasizes that RMSF should be considered in the differential diagnosis of any obscure febrile illness even in nonendemic areas.
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PMID:Viscerotropic Rocky Mountain spotted fever in southeastern Texas: report of a survivor with atypical manifestations and multiple organ failure. 271 89

A phase I study with recombinant human tumor necrosis factor alpha (rhuTNF-alpha; Knoll AG, Ludwigshafen, FRG) in patients with advanced malignant disease was undertaken to evaluate drug toxicity (organ specificity, time course, predictability, reversibility, maximal tolerated dose), effectiveness, antigenicity and pharmacokinetics. TNF was administered as a test dose followed by daily i.v. infusions for 5 days, every 3 weeks (single i.v. infusion lasting 10 min, TNF dissolved in 50 ml 5% human albumin). Dosage was increased in groups of 3 or 4 patients from 0.04 mg/m2 to 0.28 mg/m2. A total of 19 patients with different cancers, including seven large-bowel carcinomas, three chronic myelogenous leukemias, three hypernephromas, two small-cell lung cancers, one malignant melanoma, one malignant lymphoma, one rhabdomyosarcoma and one fibrosarcoma were treated. Major side-effects were chills and fever (maximum 40.4 degrees C, median 38.7 degrees C, 19/19), headache (12/19), nausea and vomiting (12/19) and pronounced (greater than 20%) hypotension (4/19). Acute side-effects could be diminished by paracetamol or indomethacin pretreatment, and with one possible exception no tachyphylaxis to TNF was noted. Mild renal toxicity was seen during TNF treatment. Pharmacokinetic studies showed a serum half-life (t1/2) ranging from 11 min to 17 min for doses from 0.04 mg/m2 to 0.16 mg/m2 and prolonged clearance with t1/2 ranging from 54 min to 70 min in the 0.20-0.28 mg/m2 dose range. No objective antitumor effects were observed in this phase I study.
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PMID:Phase I study of recombinant human tumor necrosis factor alpha in advanced malignant disease. 272 Jul 7

About 5 weeks after the beginning of the outbreak of Ebola virus fever in Yambuku, Zaire, several acute cases of the disease were observed. All of those affected had the following common signs and symptoms: sudden onset of high fever, with chills, headache, myalgia, anorexia, nausea, abdominal pain, sore throat, expressionless face, and profound prostration. In some cases, on around the fifth day of the acute phase, the appearance of an exanthematous rash on the trunk announced the hemorrhagic manifestations: hemorrhagic conjunctivitis, bleeding ulcerations in the mouth and on the lips, gingival bleeding, hematemesis, and melena; epistaxis, ear bleeding, hematuria, and postpartum hemorrhages were also reported. All these hemorrhagic cases had a fatal outcome within about a week. The hemorrhagic manifestations were less severe in the cases that occurred by the end of the outbreak than in the first reported cases. Hemorrhagic manifestations were less frequent and less severe, or even absent, in the nonfatal cases (convalescents, serologically confirmed). No biologic investigation of the hemostatic impairment could be performed under the emergency conditions of this field study.
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PMID:Firsthand clinical observations of hemorrhagic manifestations in Ebola hemorrhagic fever in Zaire. 274 10

We studied all patients with community-acquired pneumonia who were admitted to our 800-bed adult acute care hospital from 1 November 1981 to 15 March 1987. The 719 patients had a mean age of 63.2 years; 18% were admitted from nursing homes, and 18% required ventilatory assistance as part of the therapy for pneumonia. Patients with nursing home-acquired pneumonia were significantly older; had a higher mortality (40% vs. 17%); were more likely to be admitted in January; were less likely to complain of cough, fever, anorexia, chills, headache, nausea, sore throat, myalgia, or arthralgia; and were more likely to be confused than those admitted from the community. Pneumonia of unknown etiology and aspiration pneumonia were more common and Mycoplasma pneumoniae infection less common among those with nursing home-acquired pneumonia. Streptococcus pneumoniae accounted for 58% of the 48 cases of bacteremia. None of the bacteremic patients received antibiotics before admission, compared with 34% of the nonbacteremic patients. Aerobic gram-negative rod bacteremia was not more frequent among nursing home patients than among those from the community. The overall mortality was 21% (8.5% for those less than 60 years of age and 28.6% for those greater than 60 years old). By multivariate analysis the following variables were significant predictors of mortality: number of lobes involved by the pneumonic process, number of antibiotics used to treat the pneumonia, age, admission from a nursing home, ventilatory support, and the number of complications that occurred while the patient was in the hospital.
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PMID:Community-acquired pneumonia requiring hospitalization: 5-year prospective study. 277 65

Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.
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PMID:A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. 278 32

Nineteen patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant tumor necrosis factor (rTNF). The rTNF was administered subcutaneously for 5 consecutive days every other week for 3 treatment weeks. The doses administered ranged from 5 micrograms/m2/day to 150 micrograms/m2/day. There was no intrapatient dose escalation. Systemic side effects of chills, fever, hypotension, nausea, vomiting, and headache were mild and self-limiting. At the maximum tolerated dose of 150 micrograms/m2/day, five of seven patients experienced moderate to severe thrombocytopenia. Mild rapid declines in total leukocyte count occurred within 60-90 min of administration of the drug, followed by a rise in the total leukocyte count by 120 min. When the total daily dose was administered in a single subcutaneous site, skin ulceration and necrosis occurred at the 100 micrograms/m2/day dose. By giving the total daily dose in two subcutaneous sites, the maximum tolerated dose increased to 150 micrograms/m2/day, and there was no further skin ulceration or necrosis. Skin necrosis occurred in the abdomen and thigh but not on the upper extremity at the 100 micrograms/m2/day dose given in a single site. There was no other significant organ toxicity. No rTNF was detectable in the serum even at the highest doses. No antibodies to TNF developed in any of the patients. The recommended dose of rTNF for Phase II trials given for 5 days subcutaneously is 150 micrograms/m2/day divided into two or more sites.
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PMID:A phase I trial of subcutaneously administered recombination tumor necrosis factor to patients with advanced malignancy. 279 95

A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 micrograms/m2/d. Dose-limiting toxicities were encountered at doses greater than 100 micrograms/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses greater than 100 micrograms/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 micrograms/m2/d, administered for two courses.
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PMID:Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. 291 29

A phase I study was carried out to test the feasibility and toxicity of infusing large numbers of autologous, alloactivated helper lymphocytes into patients with metastatic melanoma. Patient peripheral blood lymphocytes (Pt-PBL) obtained by lymphopheresis and expressing the helper phenotype BT5/9 were separated and stimulated for 48 or 72 h with a pool of PBL from four to six healthy donors. Patients were then infused with such activated lymphocytes over a 2-3 h period. A total of 4 phereses and infusions (2/week for 2 weeks) were carried out for each cycle in each patient. Of the five patients treated, two received a second round of infusions. Infusion of autologous PBL stimulated in vitro for 48 h caused chills, fever, headache, and increased blood pressure. All symptoms disappeared in 2-3 h and were easily controlled by appropriate therapy. When lymphocytes were given after 72 h of allostimulation, no or very mild toxicity was observed. Serum chemistry, coagulation, autoimmunity, and urine analysis showed no gross abnormalities during therapy or follow-up of the patients. Immunological parameters (OKT4/OKT8 ratio, NK activity and cytotoxic T cell activity to autologous melanoma) were evaluated before starting the therapy, during its course and during the 3 to 6 months follow-up. The OKT4/OKT8 ratio increased significantly but transiently soon after the first course of infusions in one of the two patients tested. NK activity increased after 75-100 days in the three patients tested and in one of them it was high even after 180 days. No correlation between NK activity and prognosis was apparent. Cytotoxicity to autologous tumor was assessed in two patients, only of one of whom exhibited an increased activity from 75 to 180 days, which was associated with a prognosis better than that of the negative patient. Five patients were treated: two had progressive disease, two had stable disease for 5 and 6 months, respectively. In the first of these patients, a new cycle of lymphocyte infusions was carried out which caused a measurable reduction of lung tumor nodules whose growth, however, resumed 4 months later. This patient died 14 months after the onset of therapy. The fifth patient had a partial regression of pulmonary and intracranial metastases after therapy, but eventually died 3 months later. These results indicate that infusion of a high numbers of autologous, allostimulated helper PBL is a feasible and safe procedure, which could therefore be used in future studies of adoptive immunotherapy of cancer.
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PMID:Systemic administration of autologous, alloactivated helper-enriched lymphocytes to patients with metastatic melanoma of the lung. A phase I study. 293 47


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