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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 13-year-old girl with osteosarcoma and pulmonary metastases developed life-threatening renal toxicity, encephalopathy, and bone marrow failure following high dose methotrexate therapy. After successful treatment, high dose methotrexate therapy was continued without further problems. Recommendations for the prevention and the current management of methotrexate toxicity are discussed.
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PMID:[(Management of acute toxicity after high dose methotrexate therapy)]. 39 13

Two children with osteosarcoma are presented in whom Wernicke encephalopathy with vomiting occurred during the chemotherapy. One of the children died with symptoms of toxic cardiomyopathy. Autopsy revealed Wernicke encephalopathy. The other child had similar symptoms (ocular signs, ataxia, somnolence). Parenteral thiamine had been given and after this therapy the child recovered from the encephalopathy. The authors emphasize the importance of the recognition of this neurological disorder occurring rarely in childhood: it can be cured with parenteral thiamine. Without thiamine treatment this condition is lethal.
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PMID:[Wernicke encephalopathy in childhood osteosarcoma]. 140 86

An animal model of intracerebral osteogenic sarcoma has been developed to evaluate blood-brain barrier disruption as an adjunct to chemotherapy of intracerebral tumors. Adult Sprague-Dawley rats (n = 225) were inoculated intracerebrally with transplantable, methotrexate sensitive, osteogenic sarcoma cells and 3 days later randomized to receive either no treatment or methotrexate with or without blood-brain barrier disruption using intracarotid mannitol. Methotrexate was administered i.v., i.p., or directly into the carotid artery (i.c.) in doses of 2.5, 10, 20, 50, or 100 mg/kg. Survival was the study's end point. Surgery, anaesthesia, or blood-brain barrier disruption with mannitol did not affect survival. However, there was a significant effect of dose and route of administration of methotrexate on survival. The shortest survival was in rats receiving no treatment in which death occurred reproducibly at 7.6 +/- 0.2 days (n = 29) and the longest survival was 12.7 +/- 0.3 day (p less than 0.001) in those given methotrexate 50 mg/kg i.c. (n = 6). The i.c. route was most effective in prolonging survival followed by i.v. and the least effective was the i.p. route of methotrexate administration. Blood-brain barrier disruption followed by methotrexate (i.v. or i.c.) was deleterious to survival (two-way analysis of variance, p less than 0.003 and p less than 0.011, respectively) and the reduced survival was in part related to early complications such as intratumor hemorrhage or possibly a methotrexate induced encephalopathy. It is concluded that this is a useful model for the study of the chemotherapy of cerebral tumors, that blood-brain barrier disruption did not appear to improve the dose-response curve but resulted in reduced survival. We caution against the use of this procedure in the treatment of cerebral tumor in humans.
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PMID:Blood-brain barrier disruption and methotrexate in the treatment of a readily transplantable intracerebral osteogenic sarcoma of rats. 311 95

An acute episode of encephalopathy after the infusion of 16 g methotrexate is reported in a 12-year-old girl with osteogenic sarcoma. The complication occurred during the 11th treatment course, when severe vomiting and diarrhea were followed by a low urine output with consecutive toxic concentrations of methotrexate in serum and cerebrospinal fluid leading to severe systemic and central nervous system toxicity. The onset of the central nervous system toxicity was acute with slurred speech, paresis of the external rectus eye muscles, ataxia, and hemiparesis, and symptoms resolved completely after 30 hours by treatment with calcium leucovorin and forced diuresis. After management of the cerebral and systemic toxicity, high-dose methotrexate treatment could be reinstituted, and was followed by no further complications. In contrast to the transient cerebral dysfunctions, probably caused by embolization of tumor tissue in the early course of high-dose methotrexate treatment, the acute neurologic syndrome observed in the current case after the prolonged use of methotrexate seemed to be related to direct central nervous system toxicity of the drug.
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PMID:Transient encephalopathy during the late course of treatment with high-dose methotrexate. 658 97

In 23 treatment courses of high-dose Methotrexate (MTX) with Leukovorin-rescue for osteogenic sarcoma serial EEG-examinations before and after MTX-infusion were done. In 11 course Vincristine had been administered additionally. Frequency-analysis of EEG-background activity was performed by computer-based FFT. At the end of the MTX-infusion EEGs were unchanged, compared with the findings before start of treatment. At 24 and 48 hours after start of infusion, there was a slight but statistically significant slowing, recognizable from an increase of the theta/alpha-ratio (median + 48%, range -7% to + 373%) and a drop of dominant frequency (median-8%, range +12% to -53%). There was a stronger trend towards normalisation in patients, not having received Vincristine. The greatest changes were found in a patient, whose serum-MTX-concentration at 24 hours exceeded the upper therapeutic limit. The EEG-findings are discussed as an equivalent of a subclinical MTX-encephalopathy. Acute encephalopathies with severe EEG-changes and morphological changes on CT have been observed in MTX-intoxications.
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PMID:[EEG-slowing after high-dose Methotrexate with citrovorumfactor-rescue. A spectralanalytic study (author's transl)]. 680 66

The mechanism of the transient encephalopathy induced by high dose systemic administration of methotrexate (HDMTX) is unknown. Metabolic and vascular hypothesis have been formulated but convincing evidence is lacking. We report the first case of vascular disturbances (thinness of cortical arteries on angiography, reversible fall down of cerebral flow and increase of carotid resistance) in a young Algerian patient treated for an osteogenic osteosarcoma. This observation might lead to the exploration by non invasive and easily repeatable techniques of the cerebral vascular dynamic in patients submitted to HDMTX and thus contributed to the elucidation of the mechanism and to the prevention of these neurological side effect.
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PMID:Cerebral arterial disturbances in a transient encephalopathy induced by methotrexate. 816 55

Defects of the respiratory chain carrying out oxidative phosphorylation (OXPHOS) are the biochemical hallmark of human mitochondrial disorders. Faulty OXPHOS can be due to mutations in either nuclear or mitochondrial genes, that are involved in the synthesis of individual respiratory subunits or in their post-translational control. The most common mitochondrial disorder of infancy and childhood is Leigh's syndrome, a severe encephalopathy, often associated with a defect of cytochrome c oxidase (COX). In order to demonstrate which genome is primarily involved in COX-deficient (COX(-))-Leigh's syndrome, we generated two lines of transmitochondrial cybrids. The first was obtained by fusing nuclear DNA-less cytoplasts derived from normal fibroblasts, with mitochondrial DNA-less (rho degree) transformant fibroblasts derived from a patient with COX(-))-Leigh's syndrome. The second cybrid line was obtained by fusing rho degree cells derived from 143B.TK- human osteosarcoma cells, with cytoplasts derived from the same patient. The first cybrid line showed a specific and severe COX(-) phenotype, while in the second all the respiratory chain complexes, including COX, were normal. These results indicate that the COX defect in our patient is due to a mutation of a nuclear gene. The use of cybrids obtained from 'customized', patient-derived rho degree cells can have wide applications in the identification of respiratory chain defects originated by nuclear DNA-encoded mutations, and in the study of nuclear DNA-mitochondrial DNA interactions.
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PMID:Nuclear DNA origin of cytochrome c oxidase deficiency in Leigh's syndrome: genetic evidence based on patient's-derived rho degrees transformants. 858 77

The cases of three children, 16, 12, and 12 years of age, who suffered sudden confusional state and cortical blindness lasting 12 to 30 minutes while under treatment with high-dose methotrexate, cyclophosphamide, and dactinomycin for a lower limb osteosarcoma are reported. Transient neuropsychologic deficits arose after the acute phase of treatment: left hemispatial neglect and constructive apraxia (Patient 1); constructive apraxia (Patient 2); and constructive apraxia and alexia without aphasia (Patient 3). The three patients recovered completely from all their deficits within the time frame of 3 hours to 2 weeks. Arterial hypertension and hypomagnesemia were found during the acute phase in all patients. In Patients 2 and 3, magnetic resonance imaging revealed increased parieto-occipital T(2) signal involving gray and white matter. In Patients 1 and 2, HmPAO-SPECT revealed parieto-occipital hypoperfusion that resolved a few days later. The alterations detected by neuroimaging were concurrent with the appearance and disappearance of the clinical symptoms. Such transient acute episodes have been named occipital-parietal encephalopathy. On the basis of our clinical, laboratory, and neuroimaging findings, an explanation for the origin of this syndrome, a migrainelike mechanism, triggered by chemotherapy-induced hypomagnesemia, is proposed.
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PMID:Transient posterior encephalopathy induced by chemotherapy in children. 1127 65

Chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, may be responsible for serious adverse effects like encephalopathy in ifosfamide chemotherapy. In this study, we demonstrate that chloroacetaldehyde, but not ifosfamide, induces cell death in human osteosarcoma Saos-2 cells and we investigated the mechanism by which this occurs. Chloroacetaldehyde above 30 micromol/l induced significant cell death in a time-dependent manner. Thiol compounds such as N-acetyl cysteine, glutathione and dithiothreitol protected the cells against chloroacetaldehyde-induced cell death, although other nonthiol compounds and the antioxidative enzymes superoxide dismutase and catalase did not, suggesting that reactive oxygen species might not mediate cell death. In cells exposed to chloroacetaldehyde, levels of both total thiols and glutathione were significantly reduced. Chloroacetaldehyde also collapsed the mitochondrial membrane potential of these cells, induced the release of cytochrome c from mitochondria to the cytosol and significantly reduced cellular ATP levels during the course of death. The mitochondrial potential collapse was also prevented by thiol compounds. Flow cytometric analyses by means of annexin-V and propidium iodide double staining and immunofluorescence staining of active caspase-3 revealed that cells subjected to a lethal dose of chloroacetaldehyde displayed features characteristic of necrosis and that caspase-3 was not activated in response to chloroacetaldehyde. Taken together, these findings suggest that Saos-2 cells exposed to chloroacetaldehyde die by necrosis resulting from a decrease in intracellular thiols, disruption of the mitochondrial membrane potential and the depletion of cellular ATP.
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PMID:Necrotic pathway in human osteosarcoma Saos-2 cell death induced by chloroacetaldehyde. 1741 23

Methotrexate (MTX) is a major cause of treatment-related acute neurotoxicity. We report on clinical and imaging findings of reversibly restricted diffusion in a patient with transient encephalopathy after high dose MTX therapy for osteosarcoma. During the chemotherapy, a 19-year-old man was introduced for the evaluation of consciousness disturbance. Neurological examination revealed confusion, inability of speak at the onset On next day, there were still difficulties in swallowing and phonation, and furthermore deep tendon reflexes were hyperactive in bilateral lower limbs with positive Babinski responses bilaterally. By the 6th day, findings at neurological examination were completely normal. Initial imaging on presentation was performed using MRI. Diffusion weighted MRI clearly indicated areas of restricted diffusion within both centrum semiovale. These abnormalities were confirmed by the diffusion tensor (DT) technique (ADC and FA map). The follow-up MRI examinations using same protocol showed resolution of the ADC and FA abnormalities but increasing T2-signal changes. Neither contrast enhancement nor atrophy was encountered. Early detection of MTX white matter injury by DT image has the potential to alert the oncologist and neurologist to this event and provide a technique by which treatment of neurotoxicity can be monitored.
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PMID:[Case of methotrexate encephalopathy: findings on diffusion tensor image and correlation with clinical outcome]. 1751 Dec 73


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