Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assessed biologic response modification at three different dose levels (0.15, 1.5, and 15 mg/m2) of interferon-gamma (IFN-gamma) administered by intravenous bolus three times weekly. A final total of 24 patients were evaluable. Dose-limiting toxicity occurred at the highest dose level (15 mg/m2) and included fatigue, leukopenia, and hepatotoxicity. Evaluation of biologic response modification included assessment of 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral mononuclear cells, measurement of serum beta 2-microglobulin and expression of beta 2-microglobulin on monocytes, measurement of monocyte HLA Class II expression (HLA-DR, HLA-DQ), and measurement of hydrogen peroxide generation by monocytes 24 h after the first and fourth IFN-gamma treatments. Significant increases (p less than 0.05) from baseline were seen at 24 h with all parameters except H2O2 generation. Except for enhancement of HLA-DR, even the lowest dose (0.15 mg/m2) augmented synthesis of 2-5A synthetase and HLA proteins. A dose-response effect was noted for changes in serum and monocyte beta 2-microglobulin levels but not for 2-5A synthetase levels or HLA Class II antigen expression on monocytes. After 4 doses administered over 9 days, most parameters remained increased when compared to pretreatment, but were not further enhanced when compared with levels attained after the first dose. The results of this study document the efficacy of IFN-gamma for biological activation over a wide dose range and are consistent with the postulate that immunoregulatory effects of biological therapeutics can be obtained in man at doses substantially less than those that are maximally tolerated. Further documentation of biologic response parameters by IFN-gamma at low doses will be necessary to determine the importance of biologic activation in relation to antitumor activity.
 ...
PMID:Induced proteins in human peripheral mononuclear cells over a range of clinically tolerable doses of interferon-gamma. 250 86

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24

Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added. This combination chemotherapy was repeated every two weeks. As a result, 35 of 52 patients were evaluable and the response rate (CR + PR) was investigated; 2/21 (9.5%) for gastric, 2/7 (28.6%) for breast, and 0% for miscellaneous. As complications for side effect, general fatigue, anorexia, nausea, vomiting and stomatitis were observed symptomatically, and leukopenia and thrombocytopenia were recognized in laboratory data as dose limiting factors.
 ...
PMID:[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients]. 271 79

Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.
 ...
PMID:Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon. 273 23

A total of 66 patients with advanced renal cell cancer received a combination of recombinant interferon alpha-2a (18 times 10(6) units subcutaneously 3 times weekly) and vinblastine (0.1 mg. per kg. intravenously every 3 weeks). Four patients were ineligible and 6 were inevaluable for response but evaluable for toxicity. There were no complete and 9 partial responses among the 56 evaluable patients, for a response rate of 16 per cent. Median duration of response was 26 weeks, with a range of 8 to 50 weeks. Responses were observed predominantly in patients with lung and soft tissue metastases. Patients who had undergone nephrectomy did not show a better response rate than those who had not. Almost all patients had a flu-like syndrome, fatigue and anorexia. Other side effects included leukopenia, nausea, vomiting, liver function disturbances and neurotoxicity. Most of the side effects were World Health Organization grade 1 or 2; no grade 4 toxicity was observed. Antibodies against interferon developed in 6 patients during the course of treatment. However, there was no relationship between the appearance of antibodies and disease progression. The combination of recombinant interferon alpha-2a and vinblastine has modest but definite activity in patients with advanced renal cell carcinoma, although the role of vinblastine is unclear.
 ...
PMID:Phase II study of recombinant interferon alpha-2a and vinblastine in advanced renal cell carcinoma. 274 39

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.
 ...
PMID:Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy. 278 85

Twenty-two patients with Stages Ia to IVa cutaneous T cell lymphoma were entered into a controlled trial of interferon alfa-2a (Roferon-A). Patients initially received either 3 million IU interferon alfa-2a, or their dosage was escalated to 36 million IU intramuscularly daily for a 10-week induction period. At the end of induction, 14/22 (64%) of patients had an objective antitumor response: three patients had a complete response, ten patients had a partial response (greater than or equal to 50% resolution of clinical disease), and one patient had a minor response. Responders included those with Stages Ia to IVa cutaneous T cell lymphoma, and remissions have lasted at least 4 to 27.5 months. Three patients progressed from a partial to complete response with further treatment, for an overall complete response rate of 27%. Acute flu-like side effects were generally minor and transient. Malaise/fatigue, depression, anorexia, and weight loss were common chronic dose-related side effects and the most frequent reasons for dose reduction or discontinuation of drug. Leukopenia was the most common laboratory side effect and was also dose-related. Recombinant human leukocyte interferon alfa-2a is an effective and well-tolerated single-agent therapy for early and advanced cutaneous T cell lymphoma.
 ...
PMID:Interferon alfa-2a in the treatment of cutaneous T cell lymphoma. 278 39

Juzen-taiho-to (TJ-48) is prepared by extracting a mixture of ten kinds of medicinal plants. This prescription has long been used traditionally against anemia, anorexia, extreme exhaustion and fatigue. TJ-48 may now provide new advantages with little toxicity in combination with chemotherapy or radiation therapy, and promising results have actually been obtained in terms of preventing leukemia in cancer patients who have taken antitumor agents. The combination of TJ-48 and mitomycin C (MMC) produced significantly longer survival in p-388 tumor-bearing mice than MMC alone, and TJ-48 decreased the diverse effects of MMC such as leukopenia, thrombopenia and weight loss. However, mechanisms of the pharmacological action are still unclear. One of the possible mechanisms of the action of TJ-48 may be some effects on immune responses. Therefore we studied the effects of TJ-48 on immune response in mice and characterization of immunologically active substances. TJ-48 augmented antibody production and activated macrophage by oral administration of TJ-48, but reduced the MMC-induced immunosuppression in mice. TJ-48 showed a mitogenic activity in splenocytes but not in thymocytes, and an anti-complementary activity was also observed. Anti-complementary activity and mitogenic activity were both observed in high-molecular polysaccharide fraction but not in low-molecular weight fraction. Of several polysaccharide fractions in TJ-48, only pectic polysaccharide fraction (F-5-2) showed potent mitogenic activity. F-5-2 was also shown to have the highest anti-complementary activity. However, the polygalacturonan region is essential for the expression of the mitogenic activity, but that the contribution of poly-galacturonan region to the anti-complementary activity is less. F-5-2 activates complement via alternative complement pathway and induces the proliferation of B cells but does not differentiate those cells from antibody producing cells.
 ...
PMID:[Chemical characterization and biological activity of the immunologically active substances in Juzen-taiho-to (Japanese kampo prescription)]. 278 80

A 74-year-old man was admitted on November 1986 because of general fatigue. His peripheral blood showed pancytopenia without immature cells since December 1985. Hematological data showed RBC 150 X 10(4)/microliter, PLT 7,000/microliter, WBC 12,000/microliter with 93.6% leukemic cells. The bone marrow smear revealed NCC 14.5 x 10(4)/microliter with 76% leukemic cells. The leukemic cells were characterized by faint staining with peroxidase stain and strong positivity for CD 13 antigen determined with immunoperoxidase method and flow cytometric analysis. The chromosomal analysis of tumor cells represented as follows: 44, XY, -3, -4, -9, -20, 2q+, 6p-, 7q-, 12q+, +2 mar. Although remarkable reduction of leukemic cells in peripheral blood was obtained one month after initiation of 19-days intravenous continuous infusion of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), he suffered from severe systemic candida infection with severe leukopenia and died. Not only advanced age but also complex karyotypic abnormality would contribute to failure of treatment in this case. The significance of complex karyotypic abnormality in acute non-lymphocytic leukemia in discussed based on the current literature.
 ...
PMID:[Complex karyotypic abnormality in an aged patient with acute myeloid leukemia (M 2)]. 279 97

In addition to the low risk of agranulocytosis, several more frequent side effects are associated with clozapine therapy. We tried to estimate the incidence of these side effects. We analysed 391 treatments in 315 inpatients, who received clozapine alone or combined with other neuroleptic and antidepressant drugs. Two thirds were combined treatments, one third were treatments with clozapine alone (i.e., no other neuroleptic, antidepressant or anticonvulsive drugs were allowed). The numbers in brackets show the incidence based on the analysis of the treatments with clozapine alone. In 49% (61%) of the treatments a rise in the liver enzyme values was observed. However, counting only the cases in which a two-fold increase over the normal values was observed, the incidence was reduced to 20% (31%). Increase in temperature was observed in 4% (6%) and leukopenia (leukocyte count under 3500/microliters) was recorded in 2% (2%). Hypotensive dysregulation (systolic blood pressure under 90 mm Hg) was observed in 25% of all treatments and pharmacogenic delirium in 8%. No cases of agranulocytosis were observed. Mean treatment duration was 56 days, mean daily dosage 257 mg. The mean age of the patients was 34 years. In the overall evaluation 71% of the treatments were classified as successful; clozapine therapy was continued after discharge in 68% of the treatments. Adverse reactions (delirium, rise in temperature, hypotension, fatigue, rise in liver enzymes) necessitated a change of medication in 17% of the treatments. Changeover to another neuroleptic drug due to ineffectiveness of clozapine was necessary in 7% of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Side effects of clozapine. 281 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>