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

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

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

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

L-asparaginase is widely used in the treatment of acute lymphoblastic leukemia in children and adults. Use of L-aspa E. Coli as well as Erwinase is not possible in all cases because of the side effects, mainly allergic reactions and disfunction of pancreas. Recently, the new form of the enzyme PEG-L-asparaginase was introduced. Binding L-asparaginase E. coli to polyethylene glycol a decreased its toxicity, extended its plasma half-live, not significantly affecting the efficacy. The aim of the study was to examine the results of PEG-L-asparaginase administration in five children with acute lymphoblastic leukemia, and the symptoms of intolerance to L-aspa E. Coli or Erwinase. There were three children with newly diagnosed ALL and two children with first relapse of ALL, treated according to New York Protocol and BFM-90 Protocol for ALL relapses respectively. PEG-L-asparaginase (Oncaspar) was administered in the dose of 2500 IU/m2. According to the protocol four children received 11 courses of treatment with the full dose of the drug. The number of doses for individual patient varied from one to six. The short-lived nettlerash was observed in one patient during two subsequent infusions of the drug. Hydrocortisone and antihistamine drugs were administered. Treatment with PEG-asparaginase was discontinued in one child, who developed dyspnea, nausea, vomiting and face rash during the third dose of the drug. Oncaspar is the valuable drug, which enabled continuation of treatment according to protocol in four out of five children with bad tolerance to routinely used L-asparaginase preparations.
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PMID:[New possibilities of treatment with PEG-L-asparaginase in patients with acute lymphoblastic leukemia sensitized to l-asparaginase E.coli and erwinase]. 1073 74

The effectiveness of intensive post-remission chemotherapy regimens for adult patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate of disease recurrence and a substantial incidence of treatment toxicity. To evaluate a potentially more effective and less toxic approach, we conducted a multicenter phase III trial of consolidation therapies comparing the standard L10M regimen with one combining the brief, intensive L17M regimen and escalating methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with previously untreated ALL were eligible. Induction therapy included vincristine, prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate administered over 36 days. Patients who achieved complete remission (CR) were randomized to receive consolidation with either the L10M regimen or with DAT (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp. The randomization was stratified by age, WBC and Ph chromosome status. Maintenance therapy was the same in both arms. Of 353 eligible patients, 218 (62%) achieved CR and 195 were randomized. The treatment arms did not differ significantly with respect to disease-free survival (DFS; P= 0.46) or overall survival (P= 0.39). Estimated DFS at 5 years was 32% (95% confidence interval (CI) 23-42%) in the L10M arm and 25% (95% CI 16-33%) in the DAT/MTX/L-asp arm. In each arm, 4% of patients died of toxicities (infection in all but one case). Infections and nausea/vomiting were somewhat more common in the L10M arm (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some reduction in nonfatal toxicities, but no significant improvement in DFS, overall survival or non-relapse mortality when compared to the standard L10M regimen.
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PMID:Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study. 1123 36

The purpose of the study was to identify the association between chemotherapy-induced nausea/vomiting and changes to the electrogastrogram (EGG) of two children suffering from leukemia. After receiving written consent/assent, the children, both with acute lymphoblastic leukemia (ALL), were recruited. One of the subjects, a ten year-old boy, was given 1.1 gm Cytarabine (intravenous infusion for six hours per day) for three days and Tropisetron 5 mg intravenous infusion for 24 hours. The other subject, an eight year-old girl, received the induction phase of TPOG 93HR chemotherapy, which included Epirubicin, Vincristin, L-asparaginase, and Prednisolone and Tropisetron 5 mg on Day 1. The EGG recordings of both patients were recorded for a total of 42 hours by cutaneous electrogastrography over a seven day period. This included two-hour and four-hour readings taken before and immediately following the administration of chemotherapy each day. The position, movements, and activities of the children while on the EGG were recorded on digital video. Four episodes of nausea and vomiting were detected during this period. Pre- and post-nausea and vomiting during the EGG were analyzed using spectrum analysis after the deletion of motion artifacts. The findings of this study indicated that two episodes of nausea were 5.3-10.3% bradygastria and 2.1-10.3% tachygastria, with 85.8% and 100% normal gastric slow waves detected by EGG during the pre-vomiting period. Tachygastria was present in 3.4% and 12.2% of the post-vomiting period of each episode. The association of artifacts with position, movement, and activities must be considered during data collection.
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PMID:[A pilot study: gastric motility and nausea/vomiting in two leukemia children receiving chemotherapy]. 1647 72


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