Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrolyte disturbances in leukemia can be the result of the disease process or drug therapy. One group of electrolyte abnormalities is related to the stage of the leukemic process. Included in this group are newly diagnosed patients who may show elevated serum potassium, phosphorus, and magnesium--a result of their release from malignant cells after cytotoxic therapy or their accumulation due to urate nephropathy. Patients in remission usually have normal serum electrolyte concentrations, but acute leukemia patients during relapse may have hypokalemia, hypophosphatemia, and hypomagnesemia. This imbalance may be related to cellular uptake of these electrolytes in the presence of inadequate dietary intake. Other factors contributing to electrolyte derangements, and related to the leukemic process, include hyponatremia and hypochloremia secondary to the SIADH, hypokalemia in acute monocytic or acute myelomonocytic leukemia due to lysozyme-induced tubular damage, hypercalcemia possibly secondary to leukemic infiltration of bone or parathyroid glands (with PTH release), or production of a PTH-like substance by leukemic cells. Nonspecific factors related to the disease process which may aggravate the electrolyte imbalance include gastrointestinal loss through nausea, vomiting, and malnutrition. The drug-related electrolyte abnormalities include cyclophosphamide- and vincristine-induced SIADH; decreased serum sodium, chloride, potassium, and calcium concentrations as a result of polymyxin B nephrotoxicity; hypokalemia and hypomagnesemia secondary to amphotericin B; hypocalcemia, hypophosphatemia, and hyperphosphaturia due to L-asparaginase-induced hypoparathyroidism; hypokalemia due to a nonreabsorbable anion effect of antibiotics in the distal tubule or changes in membrane ionic transport of all cells by large doses of antibiotics. Electrolyte disturbance in leukemia thus have a multifactorial pathogenesis which can best be delineated according to the stage of the leukemic process and the drugs being used. Recognition of the cause or causes in a particular patient is essential for an effective approach to management. This review emphasizes the need for routine measurement of serum electrolytes during all phases of the leukemic process.
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PMID:Electrolyte and acid-base disturbances in the management of leukemia. 26 90

Between 1984 and 1987 14 patients with acute non-lymphocytic leukemia were treated with sequential high-dose cytosine arabinoside in combination with asparaginase. Twelve patients were suffering from refractory leukemia; in these patients complete remissions were achieved in 58%. The efficacy of this schedule was much better in patients with substantial leukemia cell reduction due to antecedent conventional therapy and no more than 25% blast cells in the bone marrow. In this subgroup complete remissions were achieved in 75% and 86% respectively, taking into account only the completed treatment courses. Beside the well-known side-effects such as alopecia, nausea, vomiting and hepatotoxicity, we observed an increase in severe infections. Three patients died of pulmonary mycosis.
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PMID:[Sequential high-dose cytarabine therapy in combination with asparaginase in acute myeloid leukemia]. 307 62

A 41-year-old male was diagnosed as acute lymphocytic leukemia (ALL) in November, 1982 and partial remission was obtained by a combination chemotherapy of LVP, DVP ABOP and VAMP. In January, 1983, peripheral blood showed an increasing number of leukemic cells and he was readmitted to our hospital. WBC count in the peripheral blood was 13,200/mm3 and an 82% ratio of leukemic cells was observed. Bone marrow aspiration showed a hypercellularity of 89.4% leukemic cells. High-dose Ara-C therapy was started at a dose of 3 g/m2 i.v. every 12 hours for 6 days. Leukemic cells in peripheral blood were rapidly decreased in number, and the nucleated cell count of bone marrow was also reduced after 3 weeks of treatment, however 95% of leukemic cells remained. Low-dose L-asparaginase was then supplemented at a dose of 2000 U for 3 days, and 2 months later complete remission was achieved. The side effects associated with this high-dose Ara-C therapy were nausea, vomiting, diarrhea, fever and conjunctivitis, although these were tolerable. These observations suggest that high-dose Ara-C combined with L-asparaginase should be added to the treatment of leukemia which is refractory to conventional chemotherapy.
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PMID:[Complete remission obtained in refractory acute lymphocytic leukemia using high-dose cytosine arabinoside combined with low-dose L-asparaginase]. 385 16

Clinical effects of sequential administration of high-dose cytosine arabinoside with L-asparaginase were studied in 5 cases of refractory acute leukemia and 2 cases of non-Hodgkin's lymphoma. A total 12 courses were carried out on these 7 patients and complete remission was obtained in 2 courses and partial remission in 3 courses. Two cases of lymphoma with pleural effusion or CNS invasion achieved partial and complete remission, respectively. The side effects associated with this sequential therapy were nausea, vomiting, diarrhea, fever and conjunctivitis, although these were tolerable. These observations suggest that high-dose cytosine arabinoside combined with L-asparaginase is a useful regimen for refractory leukemia and lymphoma.
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PMID:[Sequential combination of high-dose cytosine arabinoside and L-asparaginase in the treatment of refractory acute leukemia and malignant lymphoma]. 386 96

The recent development of chemotherapy in the treatment of cancer and leukemia requires that all practitioners involved have a thorough knowledge of the sometimes life-threatening side-effects of chemotherapeutic agents. All these agents, whether used alone or in a combination, carry a risk because of their lack of specificity which make active on normal cells, especially those with a rapid turn-over such as the hematopoietic cells or the cells of the digestive tract. Prior to the prescription of a chemotherapeutic regimen, the acceptable risk must always be clearly defined, according to the seriousness of the disease and to the patient's age, physical condition and psychological status. During the course continuous monitoring adjusted to the specific toxicity of the agents used is requisite. More or less prominent asthenia and weight loss are common, as the result of various physiopathological mechanisms. Digestive disorders may consist only of nausea and emesis or include mucosal lesions with diarrhea as the main feature. Vincristine and vindesine are responsible for constipation. Hepatic toxicity, which is less common, is usually due to L-asparaginase. Transient hair loss is the most frequent cutaneous side-effect. Hyperpigmentation, photosensitivity, nail lesions, cellulitis and ulcerations may occur, as well as specific lesions with bleomycin. High fever during injection often occurs with this last agent.
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PMID:[Complications of antitumor and antileukemic chemotherapy. 1]. 629 36

Dural sinus thrombosis developed in two children with acute lymphoblastic leukemia during induction treatment with vincristine sulfate, prednisone, and asparaginase. Headache, nausea, emesis, and lethargy were the presenting signs. The diagnosis was confirmed by arteriography. The cause is presumed to be secondary to hypercoagulability due to asparaginase-induced antithrombin III deficiency. The patients received anticoagulation therapy and recovered completely. Only two of the six reported patients without heparinization survived.
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PMID:Dural sinus thrombosis in children with acute lymphoblastic leukemia. 694 95

Phase II clinical trials of L-asparaginase of leunase manufactured by "Kyowa" (Japan) was performed in cooperation by 5 institutions of the USSR on 49 patients with various forms of hemoblastosis, including 15 patients aged 1 to 15 and 34 patients aged 16 to 75. The drug was used in a daily dose of 200 IU per 1 kg body weight administered as intravenous drips daily for 2--3 weeks. The daily dose was divided into 2 doses administered at an interval of 12 hours. The efficiency of the treatment did not depend on the patients' sex. Significant efficiency of leunase was observed in children with acute lymphoblastic leukemia (85.7 per cent). The use of the drug in treatment of adults with systemic malignant blood affections was less effective. Some effects recorded in patients with generalized forms of hematosarcoma were transient. The following side effects were noted: nausea, vomiting in 8 children and 13 adults, allergic reactions in the form of pruritus and rashes in 8 adults, impairment of liver and pancreatic functions in 2 children and 1 adult. Acute pancreatonecrosis was recorded in one child. The effect on the peripheral blood was insignificant. Leunase has probably no advantages as compared to other L-asparaginase preparations.
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PMID:[L-asparaginase study results (phase II of the clinical trials)]. 699 70

The polyethylene glycol (PEG) adduct of Escherichia coli L-asparaginase was administered intravenously to 4 patients with chemotherapy refractory cancers. The PEG-enzyme in plasma exhibited a half-life of 16-25 days. Doses of 250IU/m2 or greater reduced plasma asparagine to undetectable levels for as long as enzyme was detectable in plasma. All doses of enzyme administered (250-1000 IU/m2) caused similar increases in plasma aspartate, i.e. no dose-response relationship. Pleural fluid and ascites contained detectable enzyme but at a value 10-15% of simultaneously drawn plasma levels. Toxicity in this small group of patients was minimal; nausea and transient fever predominated. There were no clinical signs of PEG-asparaginase-induced pancreatitis, renal dysfunction, hypocalcemia and hyperglycemia. No patient developed evidence of a PEG-asparaginase allergic reaction; no patient formed antibodies to asparaginase or PEG-asparaginase. Two patients with large cell lymphoma showed a partial response to treatment.
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PMID:Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct. 704 23

We treated 13 adult patients with acute leukemia or chronic myelocytic leukemia (CML) in blast phase using succinylated Acinetobacter glutaminase-asparaginase (SAGA) administered on a daily dose schedule. SAGA reduced the peripheral blast count in two patients with acute lymphoblastic leukemia and two with blastic CML; however, no patient achieved either complete or partial remission. Marked central nervous system toxic effects (encephalopathy and coma) were observed, limiting treatment in patients whose disease appeared responsive; this effect finally prompted early discontinuance of the trial. Other toxic effects observed included nausea, hyperglycemia, and respiratory alkalosis. Hypersensitivity reactions to the enzyme were not seen. Pharmacologic analyses showed that prolonged blood glutamine depletion was achieved only by daily enzyme administration; however, we noted the importance of performing amino acid analysis on blood which was deproteinized immediately following phlebotomy. Our results demonstrate excessive central nervous system toxicity when glutaminase-asparaginase is administered on a daily schedule. Because of this effect, we propose that future trials of similar enzymes be limited to short courses of enzyme therapy, possibly with the addition of antimetabolites or amino acid analogs, which could enhance the antitumor effect without increasing toxicity.
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PMID:Clinical evaluation of succinylated Acinetobacter glutaminase-asparaginase in adult leukemia. 704 29

Succinylated Acinetobacter glutaminase-asparaginase (SAGA) has broader antitumor activity than Escherichia coli L-asparaginase in experimental systems; moreover, drug resistance does not develop in tumor cell lines initially sensitive to this enzyme. We have investigated the pharmacology and toxicology of SAGA after both single-dose and serial daily dose injections in 20 adult patients. Glutaminase activity in plasma after i.v. injection of single doses did not follow simple first-order kinetics (half-life during the initial 24 hr was 21 +/- 9 hr. A linear relation was observed between increasing doses of SAGA and resultant levels of plasma enzyme activity and blood glutamate. Assay of whole blood which had been deproteinized immediately following phlebotomy showed that single doses of SAGA lowered glutamine only transiently to nondetectable levels; serial daily doses were required to achieve and maintain continuous glutamine depletion. Reversible depression of the central nervous system, ranging from encephalopathy to coma, occurred in a dose-related manner and was dose limiting. Other prominent reactions included respiratory alkalosis, hyperglycemia, nausea, and vomiting. Transient antitumor effects were noted in two patients with solid tumors and in two patients with leukemia. SAGA causes considerable neurotoxicity in adults which requires close patient monitoring. Phase II studies in leukemic patients are in progress.
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PMID:Phase I evaluation of succinylated Acinetobacter glutaminase-asparaginase in adults. 743 89


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