Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 49 children with acute lymphoblastic leukemia serial EEGs were performed during the course of treatment. Therapy in the first four weeks consisted of: Prednisone, vincristine, daunorubicine and L-asparaginase. In the second month 6-mercaptopurine, cytosin-arabinoside, cyclophosphamide, methotrexate-i. th. and cranial irradiation were administered. Maintenance-therapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate i.v. Before treatment only 24% of patients showed normal EEG-findings, whereas 57% presented sly induced by leukemic infiltrations and partly due to the impaired clinical state. At the end of the first phase of therapy, the combined toxicity of vincristine and L-asparaginase led to the finding of 23% severely and 37% moderately slowed EEGs. Slightly disturbed EEGs were found in 29% and normal ones in 11% of children. Regression occurred duirng the phase of CNS-prophylaxis. At its end 37% of recordings were normal and 57% slightly abnormal. After maintenance-therapy of 1/2 to 1 year duration, there were 65% normal findings. Moderate and severe disorders were no longer demonstrated. Paroxysmal activity developed twice, each during the first phase of therapy and accompnaying convulsions. In both cases we saw slowing of background-activity and signs of increased excitability still months after. In one of these patients, the probable cause was a vincristin-encephalopathy, the cause of the second case remained unknown. EEGs of two furtehr patients with rubella-encephalitis and subarachnoideal hemorrhage exhibited severe unspecific changes.
...
PMID:EEG-changes during intensified induction-therapy of acute lymphoblastic leukemia. 29 91

Current therapy has resulted in improved prognosis in previously untreated children with acute lymphocytic leukemia less than 16 years of age. The induction phase of chemotherapy should include the use of at least prednisone and vincristine. This combination should result in a hematologic remission in about 90 per cent of the patients. The efficacy of the addition of either L-asparaginase or daunomycin, the consolidation phase or the periodic readministration of induction drugs has not been established. Specific central nervous system treatment, early in the course of therapy, is an integral component of recently reported effective protocols. Several modalities of prophalytic central nervous system therapy have been utilized. These include cranial irradiation plus intrathecal methotrexate, craniospinal irradiation and intrathecal methotrexate alone. An encephalopathy syndrome has been reported as a complication in 10 to 66 per cent of these patients. The most effective form of central nervous system therapy, associated with the least toxicity, has not been established. Maintenance chemotherapy should include a combination of two or more drugs. Complications are numerous, and include hematopoietic depression, immunosuppression, overwhelming infections, and, possibly, the development of secondary primary cancers. In the most successful protocols maintenance chemotherapy has been administered for 3 years. Because of the potential significant toxicity there is a need to define the optimal duration of maintenance therapy. Psychological complications developing in a patient with a disease now considered a potential long term chronic illness, rather than a disease once considered universally fatal, are also discussed. The possibility of an immunologic deficiency allowing for the initial development of acute lymphocytic leukemia and the role of immunotherapy are presented. While the use of intensive combination chemotherapy and specific central nervous system prophylactic therapy have resulted in an improved prognosis in childhood acute lymphocytic leukemia, because of a significant incidence of failures, a standardized single form of therapy has not been established.
...
PMID:The definitive treatment of children with acute leukemia. 78 18

Between 1972-1977, 92 patients with acute lymphoblastic leukemia, between 0 and 14 years of age, were treated with C2-72 and D-74 protocols. Induction treatment consisted of prednisolone (PRED)-vincristine (VCR) with the addition of daunorubicin (prot. C2-72) or asparaginase (prot. D-74). In both protocols, preventive therapy on the CNS consisted of cranial irradiation (24 Gy) and 5 doses of methotrexate i.t. (MTX). For the maintenance phase in protocol C2-72, three combinations: mercaptopurine (MP)-MTX, MP-Ara.C and MTX-cyclophosphamide, were sequentially administered for 3 years, with reinductions of PRED-VCR every three months. In protocol D-74, only MP-MTX was used for 3 years; the random half of the patients also received "reinductions". In protocol C2-72, BCG was administered by scarifications for 2 years to patients in remission after 36 months; in D-74, the random-half patients received BCG and irradiated allogeneic blasts for one year. The other half of the patients received no other treatment. The overall disease-free survival rate is 45.6% with a duration of between 84 and 156 months. Only one death occurred after 7 years. In protocol C2-72, 9 of 26 initial patients (34.6%) and in protocol D-74, 33 of 66 initial patients (50%) are still alive, off treatment and with no sign of disease. Ten patients (10.8%) died in continuous remission of infection (8) or toxic encephalopathy (2); five deaths were caused by "Pn. carinii". The incidence of meningeal relapse was 11% and isolated testicular relapse in males 15.7%; moreover, in 6 of the 22 boys in remission, programmed testicular biopsy showed interstitial leukemic infiltrates. Analysis of initial risk factors permitted the establishment of a risk index (r.i.): in cases with a r.i. below 3 (76% of cases) the survival rate was 53%; in the group with a higher r.i. (24%), it was 22%. Further conclusions of this study were: the lack of effectivity of "reinductions" and immunotherapy and proof of a higher rate of relapses in males mainly owing to isolated testicular relapse.
...
PMID:[Acute lymphoblastic leukemia in children. Long survivals obtained with protocols C2-72 and D-74 (1972-1977)]. 351 41

A number of neurological disturbances occur during the treatment of childhood malignancies with cytotoxic drugs like vincristine, methotrexate, cytosine-arabinoside, cyclophosphamide, asparaginase and others. Neurological complications range from peripheral neuropathy, myopathy, myelopathy to encephalopathy with methotrexate induced encephalopathy leading to permanent brain damage or death in most cases. Irradiation of the brain can produce transient or permanent brain damage by a direct effect on nervous tissue and by altering the blood brain barrier or the blood circulation. The many conflicting reports concerning the quality of life of long-term survivors of childhood leukaemia do not give sufficient data for final conclusions. The experiences we have encountered over the past ten years seem to confirm the optimistic echo from others. There is, however, an urgent need for a prospective study to answer the all important question: will a child suffering from leukemia emerge physically and mentally unharmed after long and aggressive treatment?
...
PMID:Therapy of acute lymphoblastic leukaemia in childhood: effects on the nervous system. 625 7

Increasingly vigorous chemotherapy of cancer including primary and metastatic central nervous system disease has resulted in prolonged good-quality survival. However, there has been an associated increase in neurotoxicity from both radiation therapy and chemotherapy. All classes of chemotherapeutic agents contain drugs that are potentially neurotoxic, often only at high doses. Mechlorethamine, the first nitrogen mustard, is not neurotoxic at conventional dosage, but at high doses, it may produce both an acute and a delayed encephalopathy. Methotrexate administered intrathecally often induces reversible aseptic meningitis, but chronic administration, either intrathecally or high-dose intravenously, may produce fatal leukoencephalopathy. 5-Fluorouracil at high dosage may cause cerebellar ataxia, but may also do so at low dosage when combined with thymidine infusions. Cytosine arabinoside at high dosage may also produce cerebellar ataxia. Vincristine produces a peripheral neuropathy, and less commonly causes both autonomic and cranial neuropathy. The enzyme L-asparaginase can produce a dose-related reversible encephalopathy. BCNU, now the mainstay of glioma chemotherapy, may combine with radiation to produce long-term cerebral atrophy. Both intracarotid and high-dose intravenous BCNU administration may cause encephalopathy. Several other chemotherapeutic agents have also been reported to cause neurotoxicity under certain circumstances.
...
PMID:Neurological complications of antineoplastic therapy. 638 4

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.
...
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.
...
PMID:Phase I evaluation of succinylated Acinetobacter glutaminase-asparaginase in adults. 743 89

We reviewed the records of 127 consecutive pediatric patients with acute lymphoblastic leukemia (ALL) to determine the incidence, timing, etiologies, and recurrence rate of seizures in this population. Patients with ALL and seizures were identified retrospectively by review of the records of all pediatric ALL patients who were diagnosed and treated during the years 1983 through March 1993 in a large tertiary-care hospital. Seventeen patients (13%) developed one or more seizures. In 16 patients, seizures occurred during antileukemic treatment, and in almost all of them seizures were related to intrathecal methotrexate (IT MTX) or subcutaneous L-asparaginase treatment. One patient who developed a seizure while not receiving chemotherapy had a history of cerebral infarctions. In 8 patients, (47%), the initial seizure episode was associated with a cerebral lesion. One or more seizures recurred in 6 patients. Four of these patients had an isolated recurrence, in 3 patients < or = 3 months and in 1 patient < or = 6 months after the initial event. Two patients (12%) with static encephalopathy and neurological deficits developed a chronic seizure disorder. There is a significant risk of acute symptomatic seizures in pediatric ALL patients. Most seizures in these patients occur during the acute treatment phase and are most frequently related to side effects of chemotherapy. The long-term recurrence risk is low; recurrence occurs most often in patients with evidence of cerebral structural lesions and neurological deficits. Long-term antiepileptic drug (AED) therapy should be restricted to such patients.
...
PMID:Prognosis and treatment of seizures in children with acute lymphoblastic leukemia. 763 3

Coagulation disorders are common in cancer patients. In patients with solid tumors, a low-grade activated coagulation can result in systemic and cerebral arterial or venous thrombosis. Cancer treatments may also contribute to this coagulopathy, which usually, but not exclusively, occurs in the setting of advanced malignant disease. There may be TIAs or cerebral infarctions. Because of the widespread distribution of cerebral thromboses, there may be a superimposed encephalopathy; sometimes this is the only sign. Concurrent systemic thrombosis is present in many patients and is a useful clue to the diagnosis. In cerebral venous occlusion, the initial symptom is usually a headache. Except for cerebral intravascular coagulation that is unassociated with NBTE, neuriomaging studies usually demonstrate one or more parenchymal infarctions. MRI or MRV may demonstrate venous thrombosis. The laboratory evidence of coagulopathy is difficult to distinguish from the asymptomatic coagulopathy that often accompanies advanced cancer, and the test results must be interpreted cautiously. NBTE can be diagnosed by transesophageal echocardiography. There is no established treatment for the thrombotic coagulopathy associated with cancer, but anticoagulation should be considered. In leukemia and lymphoma, the coagulopathy is typically acute DIC that can lead to systemic and brain hemorrhages. It is especially common in acute myelogenous leukemias. The clinical signs of cerebral hemorrhage are fulminant and may be fatal. The bleeding usually occurs in the brain or subdural compartment, and rarely in the subarachnoid space. The diagnosis can be suspected by the clinical setting and by systemic thrombosis or hemorrhage. It can be established by examination of the peripheral smear, the platelet count, and tests of coagulation function. Therapy of acute DIC is controversial and should be individualized for the clinical setting. Cerebrovascular disorders can complicate metastatic or primary tumor in the brain, skull, dura, or leptomeninges. The clinical signs of infarction are indistinguishable from other causes of stroke, except that tumor-related venous occlusion will usually first produce signs of increased intracranial pressure. The diagnosis of tumor-related infarction can usually be established by neuroimaging studies that show infarction and may show extracerebral sites of tumor. CSF examination is useful in diagnosing leptomeningeal metastasis. A search for lung or cardiac tumor should be performed when embolic tumor infarction is suspected. Primary or metastatic tumors in the brain or dura may hemorrhage, producing the initial clinical signs of the brain tumor or a change in chronic signs induced by the tumor. There are helpful clues to a neoplastic hemorrhage on brain CT or MRI scans. The brain hemorrhage may require evacuation and the underlying tumor will usually require additional antineoplastic treatment. Hyperleukocytosis (extreme elevation of the cell count) in acute myelogenous leukemia is a less common cause of brain hemorrhage in recent years because of improved methods to lower the cell count. Cerebral arterial or venous thrombosis is sometimes the result of cancer therapy. The attribution of thrombosis to chemotherapy in many published cases is only speculative, because carefully conducted prospective studies that include investigation for other thrombotic causes are not available. The best-known associations with thrombosis are L-asparaginase, which is typically used in the induction therapy of acute lymphocytic leukemia, and combination hormonal therapy and chemotherapy for breast cancer. Radiation to the head and neck, typically administered for head and neck epithelial cancers or lymphoma, may result in delayed carotid atherosclerosis. The distribution of stenosis or occlusion is within the radiation portal and is typically more extensive than is atherosclerosis that develops in the absence of radiation. Small clinical series suggest that surgical treatment is equally effective as in nonirradiated carotid atherosclerosis. In children, the cerebral vessels can be affected by brain radiation resulting in stenosis or occlusion. Brain hemorrhages can result from chemotherapy effects on the hemostatic system or a microangiopathic anemia. Hemorrhages from radiation-induced vascular abnormalities are rare. Opportunistic infections, especially fungal infections, can complicate cancer or its treatment. Septic cerebral emboli may result in focal cerebral signs, seizures, or encephalopathy. Sometimes there is an associated hemorrhagic vasculitis or cerebritis. Rarely, mycotic aneurysms may bleed. A high index of suspicion is needed to diagnose fungal infection because of the difficulty in culturing the organism from the blood or CSF. A clinician can usually establish the cause of stroke in the cancer patient by performing a careful review of the clinical setting--including the type and extent of cancer and the type of antineoplastic therapy--in which the stroke occurred. Systemic thrombosis, embolism, or hemorrhage can be a clue to the cause, and appropriate neuroimaging and coagulation studies to aid in the diagnosis are available. Therapy may ameliorate symptoms or prevent further episodes. The identification of one of these unusual stroke syndromes that leads to the diagnosis of an occult and treatable cancer can be particularly rewarding.
...
PMID:Cerebrovascular complications in cancer patients. 1269 Jun 49

L-asparaginase is frequently used in combination therapy for the treatment of lymphoid malignancies. We report 5 children aged between 8 and 14 years with neurologic complications presenting with headache and seizures during the first three weeks of L-asparaginase treatment. Three patients had venous thrombosis, one presented a parenchymal hemorrhage, and one showed a peculiar encephalopathy with extended cortical and subcortical lesions suggesting a neurotoxic reaction. Decreased fibrinogen and antithrombin III levels were found. Early MRI is critical even in cases with mild neurologic symptoms. Diagnosis should be followed by early cessation of l-asparaginase application.
...
PMID:Cerebrovascular complications of L-asparaginase in the therapy of acute lymphoblastic leukemia. 1279 28


1 2 3 Next >>

---